Abstract: Objective　To investigate the correlation between HBV-DNA level, sterol O-acyltransferase (SOAT1) expression and tumor differentiation of hepatocellular carcinoma. Methods　The clinical and HBV-DNA level data from 58 cases of HBV-associated hepatocellular carcinoma were collected, and the cancer tissues and their paired paracancerous tissues were collected to detect SOAT1 expression by immunohistochemistry and evaluate tumor differentiation. Correlation was statistically analyzed using chi-square tests. Results　The high-level rate of HBV-DNA in the SOAT1 high expression group was 81.1% (30/37) compared to 19.1% (4/21) of the SOAT1 low expression group, with statistical significance, and there was also a correlation between SOAT1 expression and HBV-DNA levels (χ2=21.253,P<0.05). In the low differentiation hepatocellular carcinoma group, the rate of HBV-DNA high levels was 71.1% (27/38), while it was 35.0% (7/20) in the well-moderate differentiation group, with statistical significance. There was also a significant correlation between HBV-DNA levels and tumor differentiation degree (χ2=7.021,P<0.05). The overall positive rate of SOAT1 expression in all collected cases was 63.8% (37/58), with no expression (0/58) detected in all paired paracancerous tissues, with statistical significance (P<0.05). Furthermore, the expression level of SOAT1 protein in cancer tissues was correlated with the degree of tumor differentiation (χ2=19.889,P<0.05). SOAT1 was generally highly expressed in the low differentiated case group, with a positive rate of 84.2% (32/38), while SOAT1 was generally low expression or no expression in HCC samples with a higher degree of differentiation, with only a few samples exhibiting high expression, with a high expression rate of 25.0% (5/20). Conclusions　There is a correlation between HBV-DNA levels and hepatocellular carcinoma differentiation degree, with higher levels of HBV-DNA detected in low differentiation tumors. Additionally, the expression level of SOAT1 is also related to the degree of differentiation of hepatocellular carcinoma, and the expression level of SOAT1 in low differentiated carcinoma is also higher. Furthermore, there is a positive correlation between HBV-DNA levels and SOAT1 expression levels, and SOAT1 is a key enzyme involved in cellular lipid metabolism. These findings suggest that HBV infection may affect the function and level of SOAT1, which may interfere with hepatocyte lipid metabolism and participate in tumor genesis and evolution.