〔Abstract〕 Objective To investigate the clinical significance and biological functions of family with sequence similarity 50 member A(FAM50 A) in hepatocellular carcinoma(HCC). Methods FAM50 A mRNA and protein were examined respectively by Real-time PCR and Western blot in 45 cases of HCC tissues and paired adjacent tissues. The expression and location were analyzed by HPA database. Oncomine and GEPIA databases were used to analyze the expression difference of FAM50 A in HCC tissues and normal liver tissues. HCC dataset was collected from The Cancer Genome Atlas database. The correlation between expression level of FAM50 A and clinicopathological features of HCC was analyed by SPSS 21.0. Relationship between expression level of FAM50 A and prognosis was analyzed by Kaplan Meier Plotter. The MethHC database was used to analyze the methylation level of FAM50 A promoter region. Moreover, the String database was used to analyze the network of proteins interacting with FAM50 A and GSEA was used to predict the possible signal pathways of FAM50 A in HCC. Results For normal tissue, the hightest expression level of FAM50 A was found in skeletal muscle, and the expression of FAM50 A in the liver ranked 37 th. For tumor tissue, the hightest expression level of FAM50 A was found in ovarian cancer, and the expression of FAM50 A in liver cancer ranked 9 th. FAM50 A was mainly located in cytoplasm, membrance, nuclear in normal liver tissue and FAM50 A was mainly located in nuclear in HCC tissue. Real-time PCR showed that FAM50 A mRNA expression level was higher in tumor tissues compared with adjacent tissues, and the difference was statistically significant(P<0.001). Western blot showed that FAM50 A protein expression level was higher in tumor tissues compared with adjacent tissues, and the difference was statistically significant(P<0.05). Oncomineand GEPIA databases showed that FAM50 A mRNA expression in HCC tissue was higher than in normal liver tissue, and the difference was statistically significant(P<0.05). FAM50 A mRNA correlated with gender(P=0.006), cirrhosis(P=0.001) and vascular tumor thrombus(P=0.010), not with age, tumor size, pathological stage, Alpha-fetoprotein(AFP) level, degree of differentiation or distant metastasis(P>0.05). Patients in FAM50 A high expression group had higher overall mortality and poorer prognosis than those in low expression group, the difference was statistically significant(P<0.000 1), and it might be an oncogene. The methylation level of FAM50 A promoter region in HCC tissue was lower than that in normal liver tissue, and the difference was statistically significant(P<0.005). The proteins interacting with FAM50 A included SF3 B3, ATP6 AP1, NSFL1 C, etc. The samples with high expression of FAM50 A mRNA showed enrichment of genes in the pathways of MAPK signaling pathway, Wnt signaling pathway, Notch signaling pathway, etc.(P<0.05). Conclusion FAM50 A is high expression in HCC tissues. FAM50 A expression level is associated with the malignant degree and poor prognosis of HCC. Moreover, it may act as an oncogene and can be used as an indicator for diagnosis and prognosis evaluation of HCC patients.