Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells. FAM83H induced expression of cyclin-D1, cyclin-E1, snail and MMP2 and inhibited the expression of P53 and P27. In hepatic tumor cells derived from Tet-O-MYC mice, the expression of mRNA and protein of FAM83H were dependent on MYC expression. Moreover, a chromatin immunoprecipitation assay demonstrated that MYC binds to the promotor of FAM83H and that MYC promotes the transcription of FAM83H, which was supported by the results of a dual-luciferase reporter assay. In conclusion, we present an oncogenic role of FAM83H in liver cancer, which is closely associated with the oncogene MYC. In addition, our results suggest FAM83H expression as a poor prognostic indicator of HCC patients.