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Objective To investigate the occurrence of basal core promoter (BCP) and pre-C mutations in patients with hepatitis B virus (HBV) infection in Gansu Province, China, and to analyze the correlation of HBV mutation and HBV genotype with primary hepatocellular carcinoma (HCC). Methods PCR-RFLP was applied to detect HBV subgenotypes, and the presence of the pre-C and BCP mutations in 62 patients with HCC, 70 patients with hepatitis B induced liver cirrhosis (LC) and 90 patients with chronic hepatitis B (CHB). Results In HCC patients, genotype C was the major genotype (70.97%). The pre-C mutation was found in 59.68%, 31.43% and 16.67% patients with HCC, LC and CHB, respectively. The frequency of BCP mutations was signiifcantly different between patients with HCC, LC and CHB (74.19%, 51.43% and 37.78%, respectively;χ2=30.727, 19.540, respectively,P < 0.01). Patients in HCC group had a higher incidence of pre-C as well as BCP mutations compared to the other groups. The prevalence of pre-C and BCP mutations was signiifcantly higher in patients with genotype C1 (44.32% and 69.32%, respectively) compared to patients with other subgenotypes (P < 0.05). Conclusions The incidence of pre-C and BCP mutations increases with disease progression. Pre-C and BCP mutations frequently occur in patients with genotype C1. HBV genotype C, pre-C mutations and BCP mutations are closely related to the occurrence of HCC.