Objective:To explore the relationship between single nucleotide polymorphisms (SNPs) located in the promoter regions of Hedgehog signaling pathway genes and the risk of hepatocellular carcinoma (HCC). Methods:A hospital-based case-control study was conducted in 1 041 patients with HCC and 1 074 cancer-free controls. Using the Sequenom Mass Array platform,we detected nine candidate SNPs and then evaluated the associations between the selected SNPs and HCC risk. Results:After adjusted by age,sex,smoking,drinking status and HBV infection,the results showed that the genotype AG of STK36 gene rs34237608 polymorphism was significantly associated with a decreased risk of HCC (AG vs. AA:OR=0.67,95%CI= 0.47-0.95;P=0.025),while the GG genotype was not (P > 0.05). In the dominant model,rs34237608 polymorphism was significantly associated with HCC risk (AG/GG vs. AA:OR=0.67,95%CI=0.48-0.95;P=0.025). No significant associations between other SNPs and HCC risk were found. Conclusion: The STK36 gene rs34237608 A>G polymorphism may contribute to susceptibility to HCC in Guangxi population.