Introduction: Synovial sarcoma translocation gene on chromosome 18-like 1(SS18L1) has been found to be associated with hepatocellular carcinoma (HCC) development and progression by chromatic structure. However, the relationships between SS18L1 polymorphism and HCC have not been studied, yet. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of SS18L1 gene are associated with HCC in a Korean population. Method: We genotyped four SNPs (rs6142970, rs6061450, rs6142969 and rs2295207) using direct sequencing in 189 HCC patients and 194 controls. Clinicians were fulfilled detailed clinical features such as cancer size, stage of cancer and radiologic morphology. To analyze the genetic data, SNPAnalyzer, and SNPStats were used. Multiple logistic regression models (codominant, dominant, recessive and log-additive) were performed for odds ratio, 95% confidence interval, and p value. Age and gender as covariates were adjusted to obtain statistical significance. Result: No SNPs of the SS18L1 gene were found to be associated with the risk of HCC development. Next, the relationships between SS18L1 SNPs and the clinical characteristics of HCC were investigated. rs6142970 was associated with tumor size, significantly (p= 0.034) Also, rs6061450 and rs6142969 were associated with HCC stage and tumor size. rs2295207 was associated with serum AFP level, significantly (p=0.042) Conclusion: In conclusion, we found that SS18L1 may have a significant role in predicting the prognosis of HCC. This is the first study to demonstrate that SS18L1 polymorphisms may be associated with susceptibility to HCC in the Korean population.