Hepatitis B virus (HBV) is a non-cytopathic virus, and the liver damage caused by its continuous infection gradually causes liver inflammation, which leads to liver fibrosis, cirrhosis, and eventually causes 80% of hepatocellular carcinoma (HCC). Liver is an important organ of metabolism in the body. The abnormal activation of oncogenes and the inactivation of tumor suppressor genes will cause changes in the level and mode of cell metabolism, which is called metabolism reprogramming. Metabolic reprogramming is a key step in the transformation from liver inflammation to cancer. In this study, the expressions of key genes of lipid metabolism in HBV-positive cells (or tissues) and control cells (or tissues) were detected by reverse transcription-polymerase chain reaction (RT-PCR), enzyme linked immunosorbent assay (ELISA) and multiple fluorescence immuno histochemistry, and on this basis, the relationship between their functions and lipid metabolism was analyzed. The results showed that in HepG2.2.15 cells with stable HBV expression and Hep3B cells with stable HBsAg expression, the mRNA expressions of lipid metabolism-related genes HMGCR, SREBP-2 and PSCK9 were significantly up-regulated, and the corresponding protein expression levels were also increased synchronously in the clinicopathological results of hepatocellular carcinoma patients. It is suggested that HBV infection leads to the high expression of corresponding metabolic genes, and HBsAg is the key protein regulating the disorder of lipid metabolism enzyme genes. By analyzing the pathological data of 365 large samples of liver cancer patients, it was found that the high expression of lipid metabolism-related genes in liver cancer tissues has a trend of poor prognosis, suggesting that the disorder of lipid metabolism may be a risk factor affecting the overall survival of liver cancer patients.