China is a country with a high prevalence of hepatitis B and liver cancer, which accounts for 50% of disease incidence and deaths worldwide. In our study, we collected a total of more than 900 patients, including two groups of cirrhotic patients with and without combined liver cancer, and investigated the risk factors for hepatocellular carcinogenesis by univariate and multifactorial regression analysis. Meanwhile, we analyzed 10 single nucleotide gene polymorphisms (SNPs) on 7 genes to study the relationship between SNPs and hepatocarcinogenesis. Our main findings were as follows: 1. We found that ineffective antiviral therapy, i.e., patients who did not undergo hepatitis B treatment or failed antiviral therapy had a high risk of hepatocarcinogenesis and was the most important independent risk factor (OR=5.923). This finding highlights the importance of timely and effective antiviral therapy in preventing the development of liver cancer in patients with hepatitis B cirrhosis. Other risk factors included alcohol consumption, family history of liver cancer, family history of viral carriage, fatty liver and age (>50 years). 2. Another noteworthy point is that among the 170 patients who achieved sustained viral suppression through antiviral therapy, more than 60 cases still developed liver cancer. The mechanism may be due to the fact that HBV can integrate with the host genome, especially oncogenes, oncogenes and telomerase genes, and eventually exert oncogenic effects. This suggests that we still need to closely monitor the occurrence of hepatocellular carcinoma even if the patient’s HBV DNA is undetectable by antiviral therapy. 3. We also found a relationship between cirrhosis and liver cancer. Chronic hepatitis and fibrosis create an immune-tolerant microenvironment of hypoxia, vascular proliferation, and increased secretion of growth factors, which together promote the transformation of atypically proliferating hepatocytes into tumor cells. We hope to find specific markers and pathogenic mechanisms for early prediction of hepatocellular carcinogenesis through our research. 4. the relationship between SNP and liver cancer. SNP is the most common genetic variant in humans, which may affect many functions of genes. we found that SNP of TLR-4, SPP-1, SOX3 and other genes are associated with the development of liver cancer in patients with hepatitis B cirrhosis. Our study also found that SNPs in the human genome also affect the risk of hepatocarcinogenesis in both drinking and non-drinking subgroups of hepatitis B cirrhotic patients. Among them, candidate gene polymorphisms of TLR-4 and STXBP5L may be hepatoprotective, while SNPs of SPP1, AP3S2, MLEC, and SOCS3 may exacerbate the risk of hepatocellular carcinogenesis.