In recent years, the incidence of malignant changes in chronic hard-to-heal wounds among outpatients has been increasing year by year, which may be related to inappropriate early treatment, delayed disease, and negligence of patients. Chronic hard-to-heal wounds usually refer to wounds that cannot heal through the normal wound healing process due to various intrinsic or external factors, and enter a state of pathological inflammatory response, resulting in wounds that are difficult to heal over time. Chronic hard-to-heal wounds are a long-standing therapeutic challenge in surgery, resulting in a high rate of disability. Common clinical lesions include burn residual wounds, recurrent ulceration of unstable scars, keloids, decubitus ulcers, varicose venous ulcers, diabetic foot, etc. The normal trauma healing process can be broadly divided into three phases: local inflammatory response phase, cell proliferation and differentiation phase, and tissue remodeling phase. The pathophysiological mechanism of wound healing is a dynamic, sequential and complex process: hemorrhage, inflammation, granulation tissue formation and tissue plasticity. However, this orderly process is disrupted by various systemic or local factors, leading to the development of chronic hard-to-heal wounds. The factors that contribute to the difficulty of wound healing are summarized as follows: malnutrition, poor tissue perfusion and ischemia-reperfusion injury, bacterial colonization, infection and necrotic tissue retention, diabetes, and cellular senescence. Under the influence of these factors, the ability of trauma repair is weakened and injury factors dominate, ultimately leading to the formation of hard-to-heal wounds. Burn residual wounds, recurrent ulceration of unstable scars, and keloid breakdowns are all processes of chronic irritation, and their malignancy also undergoes the chronic ulcerative stage of recurrent and long-lasting ulceration of the wounds. Chronic stimulation has an important significance in the occurrence of cancer of long-lasting trauma and unstable scars, so patients should avoid mechanical, chemical and thermal stimulation of the affected area, preferably wear cotton products for intimate clothing, try to avoid repeated pulling, rubbing, ulceration and infection, etc. Burn scar cancer is important in prevention. Any deep burns of degree II or above should be chipped, scabbed and implanted as early as possible to make the trauma heal stably as soon as possible. If the scar is unstable and forms chronic and recurrent ulcers that do not heal for a long time, it should be treated by surgery as early as possible. In addition, medical stimulation such as radiotherapy or harmful chemicals should be avoided for burn scar area to avoid inducing burn scar cancer. For the treatment of burn scar cancer, radiotherapy and chemotherapy are less effective, and the main treatment is surgery (extended radical excision). Diabetic patients are often associated with delayed trauma angiogenesis, neuropathy and infection, which predispose to the formation of hard-to-heal wounds. Possible mechanisms include dysregulated NO levels and decreased levels of various growth factors that stimulate angiogenesis, such as vascular endothelial growth factor (VEGF), nerve growth factor (NGF), and basic fibroblast growth factor (bFGF). Increased sugar content, accumulation of reactive metabolic intermediates, and increased reactive oxygen radicals in the local tissues of diabetic skin are more recognized pathological changes, while changes in cell proliferation and apoptosis due to metabolic disorders are involved in the occurrence and development of diabetic nephropathy, neuropathy, retinopathy, and trauma refractory to healing. Blood glucose control, improvement of tissue growth environment, and surgical treatment if necessary. Decubitus ulcers and pressure sores are a result of long-term local tissue pressure, tissue degeneration and necrosis, cellular senescence, long-lasting trauma, sinus tract formation, continuous exposure of tissues to chronic refractory trauma exudate, and secondary necrosis of surrounding tissues. It has been documented that fibroblasts in several types of refractory wounds including decubitus ulcers and varicose venous ulcers exhibit senescent features. Senescent cells not only respond poorly to normal trauma healing stimuli and occupy limited trauma space, resulting in non-healing or even malignant trauma. Bacterial load, infection and necrotic tissue retention are mutually dependent. Traumatic exudate and necrotic tissue not only serve as a good culture medium for bacteria, but also constitute a barrier for bacteria to evade the host immune response and increase the chance of infection. They also release lysozyme and bacterial toxins that attack the adjacent normal tissue around the wound and prevent the movement and re-epithelialization of cells involved in wound repair. In addition, incomplete debridement and dressing changes and dry crust formation on the wound surface delay healing. Both bacterial load and infection can increase inflammatory toxins and protein hydrolases, prolonging the inflammatory response and increasing necrotic tissue. It is important to note that bacterial load and infection are different. Bacterial load refers to proliferating bacteria that are numerous enough to impair wound repair and do not necessarily lead to infection. Infection puts the organism in a hypermetabolic state and sepsis, which will make wound healing more difficult. To prevent the development of malignant changes in chronically refractory wounds, it is crucial to repair the wounds as soon as possible. Traditional wound treatment techniques include debridement, dressing exchange, scabbing, wound decompression, and treatment of underlying lesions. Since the formation of difficult-to-heal wounds is often the result of multiple factors, it is desirable to use targeted and comprehensive treatment in order to improve the efficacy of the treatment. In recent years, the level of treatment for chronic refractory wounds has gradually improved with the continuous advancement of basic research, including the study of the role and interaction of various cytokines and their receptors, and the application and maturation of various new therapeutic measures. In particular, the application of skin substitutes, free or tipped flap surgery, growth factors, and negative pressure treatment techniques for wounds. With the in-depth understanding of the mechanism of difficult to heal wounds and the healing process of wounds, as well as the application and maturation of various effective growth factor delivery techniques, new medical materials and new techniques for wound treatment such as negative pressure wound treatment, targeted treatment is expected to become a reality.