Abstract: Objective To study the association between single nucleotide polymorphism in exonic and flanking sequence of the human HLA-F adjacent transcript 10(FAT10) gene and susceptibility of hapatocellular carcinoma(HCC). Methods A total of 522 subjects,including 268 healthy controls and 254 patients with HCC were recruited.Genotyping was done by DNA sequencing.The odds ratios(ORs) and 95% confidence intervals(CIs) were calculated by unconditional logistic regression model to estimate the risk of FAT10 SNPs to development of hepatocellular carcinoma.Haplotypes distribution was estimated by haploview software. Results We identified 10 SNPs in both HCC and healthy subjects.The -143 A/G,-121 A/G,+3476 T/C,+3607 T/C,+3620 C/G and +3809 G/T genotypes were associated with a decreased risk for HCC(all P<0.05),but no SNPs were associated with disease clinicopathology(all P>0.05).Estimated by haploview software,genetic linkage disequilibrium existed both in the patients and the controls AATTTCG,AATCTCG,GGCTCGT and AGCTCGT were four most common haplotypes.Haplotypes GGCTCGT and AGCTCGT were related to reduced HCC risk(OR=0.41,95%CI=0.24~0.70,P<0.05 and OR=0.43,95% CI：0.22~0.983,P<0.05,respectively),while the haplotype AATTTCG was involved into increased risk(OR=1.64,95% CI：1.24~2.17,P<0.05). Conclusion The FAT10 gene SNPs may be involved in the susceptibility of HCC,while further research is required to confirm this hypothesis both in large sample size and different ethnicity.