To investigate the clinical significance, biological function and the precise mechanism of action of FAM134B in HCC pathogenesis, we examined the FAM134B expression in HCC and found that FAM134B is downregulated in HCC, and FAM134B expression inversely correlated with the clinicopathological features and overall survival (p = 0.026), relapse-free survival(p = 0.0029), progression-free survival(p = 0.0089) and disease-specific survival(p = 0.015) of HCC patients, suggesting that FAM134B may be associated with the progression of HCC. This evidence concerns the gene RETREG1 and hepatocellular carcinoma.