Abstract: Objective To investigate the relationship between aberrant promoter CpG islands methylation status of secreted frizzled related protein 1 (SFRP1) and long intersper sed nuclear element 1 (LINE1) gene and clinicopathologic parameters to determine their prognosis value for hepatocellular carcinoma (HCC). Methods 105 cases of HCC and 50 cases of normal people plasma were collected, and then the promoter hypermethylation status of SFRP1 and hypormethylation status of LINE1 were examined by methylation specific PCR (MSP); The relationship between SFRP1/LINE1 methylation status and patients’ clinicopathologic factors was analyzed; The association between SFRP1/LINE1 methylation status and disease-free survival and overall survival was analyzed by Kaplan-Meier curves, the log-rank test, and multivariate Cox regression. Results SFRP1 gene promoter CpG islands hypermethylation and LINE1 gene promoter CpG islands hypomethylation were found in 59.05% (62/105) and 66.67% (70/105) of 105 cancerous plasma cases, repectively, SFRP1 hypermethylation status and LINE1 hypomethylation status in plasma of HCC account for 43.81%(62/105) and no positive methylation cases were detected in normal cases; The hypermethylation status of SFRP1 and hypomethylation status of LINE1 gene were related with HBsAg and α-fetoprotein (AFP) level; There was statistically significant difference between CpG islands hypermethylation of two genes and disease-free survival rate and overall survival rate; The group patients with SFRP1 hypermethylation positive and LINE1 hypomethylation positive demonstrated the worst prognosis while the group with SFRP1 hypermethylation negative and LINE1 hypomethylation negative had the best prognosis. Conclusion The promoter methylation of SFRP1 and LINE1 is correlated with the occurrence and development of HCC. SFRP1 and LINE1 might be potential and reliable biomarkers for predicting prognosis in HCC patients.