Hepatitis B virus (HBV) DNA is prone to mutations because of the proofreading deficiencies of HBV polymerase. We have identified hepatocellular carcinoma (HCC) survival-associated HBV mutations in the X protein region of HBV DNA. In the present study, we extend our research to assess HCC survival-associated HBV mutations in the HBV precore/core (PreC/C) region. The PreC/C region was amplified and sequenced and the HBV mutations were identified according to the NCBI database (http://www.ncbi.nlm.nih.gov/genome/5536). The relationships between the mutations in the PreC/C region and HCC survival were analyzed. Survival curves were generated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. After adjusting for clinical characteristics, the 1915, 2134, 2221, 2245 and 2288 mutational sites were identified as statistically significant independent predictors of HCC survival by multivariate survival analysis using a Cox proportional hazards model. In addition, the mutational site of 1896 was identified for its association with survival at a borderline significance level. A total of five mutations in the precore/core region were identified as independent predictors of postoperative survival in HCC patients. The analysis of HBV DNA mutations may help identify patient subgroups with poor prognosis and may help refine therapeutic decisions regarding HCC patients.