【Abstract】 Objective To investigate the relationship between the mutations in exon 3 of CTNNB1 and hepatocellular carcinoma (HCC). Methods Paired tumor and normal tissue samples of 100 HCC patients were collected, DNA from the tissue at region of exon 3 of CTNNB1 was amplified by PCR, the sequencing technique was applied for assessment of somatic mutation in the local, immunohistochemical assay were used to characterize βcatenin expression in the paired tissue samples if mutations were detected.furthermore, the relationship between the mutations and the clinicopathological features in HCC patients was analyzed. Results 2 missense mutations ( p.D32V and p.H36P) in exon 3 of CTNNB1 were detected in 3 HCC patients (3%), in whose tumor tissues aberrant expression rate of βcatenin were significantly higher than that in normal tissues. No significant correlation was found between the mutations in exon 3 of CTNNB1 and clinical characteristics（P＞005）. Conclusion Mutations in exon 3 of CTNNB1 are infrequently mutated in HCC patients. It may play a function role in the development of HCC, further studies are needed to fully understand all the mutations and pathways of the gene.