The clinical manifestations of Crohn’s disease are diverse and lack specificity. Although there are many tests available, the early diagnosis rate is low, and some literature reports that only 28.2% of people are clearly diagnosed before surgery, and the preoperative misdiagnosis rate is 69.4%. The main diseases to be differentiated include appendicitis, mesenteric lymphadenitis, abdominal tuberculosis, intestinal malignancy, radiation enteritis, leukoaraiosis, ulcerative colitis, non-granulomatous ulcerative jejuno-ileitis, ischemic enteropathy, amoebic enteritis and pelvic inflammatory disease. In particular, the differential diagnosis between intestinal tuberculosis, intestinal lymphoma and Crohn’s disease should be emphasized. As the first two diseases are also easy to be misdiagnosed clinically and the treatment is contrary to Crohn’s disease, once misdiagnosed and mistreated, it will not only delay the treatment, but also aggravate the disease and produce irreversible and serious consequences. In addition, patients with Crohn’s disease may be combined with intestinal tuberculosis due to long-term malnutrition or use of immunosuppressive drugs, or with malignant lymphoma due to the stimulation of chronic inflammation and side effects of drugs. Therefore, intestinal tuberculosis and intestinal lymphoma must receive sufficient attention in the diagnosis and treatment of Crohn’s disease. Every patient with Crohn’s disease should be routinely screened for tuberculosis before a definitive diagnosis is made. In addition to the clinician’s judgment of the disease, chest radiographs and a series of laboratory tests should be performed, including tuberculin tests, Mycobacterium tuberculosis polymerase chain reaction (TB-PCR), and tuberculosis infection T-cell spotting test (T-SPOT test). The differentiation of intestinal lymphoma from Crohn’s disease relies on pathological examination, including endoscopic sampling or pathological examination of surgically excised specimens, and immunohistochemical staining can clarify the typing and provide reference for the development of chemotherapy regimens. The final diagnosis of Crohn’s disease cannot be made without pathology, and the typical pathological changes are chronic focal inflammation and patchy inflammation, irregular crypt and non-caseous granuloma formation. However, due to limitations in the volume and scope of endoscopic specimens, typical pathological specimens are not available in many cases, and thus pathological findings can only be reported as chronic inflammation.