Background and Aim Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide.Most hepatocellular carcinomas develop in the background of the advanced liver fibrosis and cirrhosis through a stepwise accumulation of various genetic alterations from cirrhotic nodule to HCC.The patterns of somatic mutations in the liver cancer and its matched cirrhotic tissues were not fully characterized..Methods We performed whole exome sequencing on liver cancer tissues,its matched cirrhotic liver tissues and peripheral blood leukocyte (PBL) in 13 patients of hepatitis B virus-associated HCC.Diagnoses of HCC cases and the matched liver cirrhosis were histologically confirmed by two pathologists.Only HCCs with the percentage of tumor cells more than 70% were used for the analysis..Results Whole exome sequencing resulted in approximate 106 million raw reads with an average coverage of 110 × in each sample.A bioinformatics pipeline was used to analyze sequencing reads and identify somatic mutations.The prevalence of somatic mutations differed significantly among HCCs.Among 6,972 non-silent mutations (i.e.,missense,nonsense mutations,splice sites and translation start sites) identified in 13 HCC patients,we found that T∶ A > A∶ T transversion showed the highest percentage of non-silent mutations,followed by C∶ G > T∶ A transversion and C∶ G > A∶ T transversion.By comparison of somatic mutations identified in liver cancer tissues and cirrhotic tissues,we found that somatic mutations were not accumulated in genes in HBVassociated cirrhotic liver tissues.Notably,two genes (TP53 and KRTAP4-3) were shown to be significantly mutated by MutSigCV analysis,suggesting that there were evidence for driver mutations of these genes contributing to the development of liver cancer.Conclusion Our study may provide an overview of patterns of somatic mutation in hepatitis B-virus associated HCC and its precancerous lesions (i.e.,cirrhosis).