Abstract: Objective To investigate the relationship between Fhit gene exon loss and risk of hepatocellular carcinoma(HCC). Methods By searching PubMed, CNKI, Wanfang Database, et al, the case-control studies about the relationship between Fhit gene exon loss and the risk of HCC were chosen. Then the Meta-analysis was conducted using odd rate(OR) and 95% confidential interval(CI) to assess the strength of association. Results Seven studies were finally chosen, including 162 hepatitis virus-related HCC cases and 170 controls(136 tumor-adjacent cirrhosis and 34 normal liver tissues). The risk of Fhit gene exon loss was higher in the HCC group than that in the control group(OR=5.02, 95%CI: 2.99-8.43, P<0.00001). Subgroup analysis showed the risk of Fhit gene exon loss was higher in HCC tissues than that in tumor-adjacent cirrhosis tissues(OR=3.55, 95%CI: 2.06-6.13, P<0.00001); and it was also higher in tumor-adjacent cirrhosis tissues than that in normal liver tissues(OR=8.23, 95%CI: 1.47-45.94, P=0.02). Conclusion Fhit gene exon loss may be notably correlated with hepatocellular carcinoma, and HBV or HCV may play a role in the development of HCC through leading the Fhit gene exon loss.