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Background: HMex-3A, an RNA-binding protein, was found to be associated with tumorigenesis. However, the roles of hMex-3A in hepatocellular carcinoma (HCC) progression remained unclear.Methods: The different expression of hMex-3A between HCC tissues and non-tumor tissues was evalu- ated using The Cancer Genome Atlas database. Thereafter, the hMex-3A expression was evaluated in HCC tissues using Western blotting and qRT-PCR. Immunohistochemistry was performed to investigate the as- sociation between hMex-3A level and clinicopathological features including prognosis in HCC patients. In addition, we used si-hMex-3A to knockdown hMex-3A in HCC cells to test Cell Counting Kit-8, colony formation, cell migration and invasion. Results: The hMex-3A expression was significantly elevated in HCC tissues. Analysis of the clinico- pathological parameters suggested that hMex-3A expression was significantly associated with patholog- ical grade ( P = 0.019) and TNM stage ( P = 0.001) in HCC. Moreover, univariate and multivariate Cox- regression analyses revealed that high hMex-3A expression (HR = 1.491, 95％ CI: 1.107–2.007; P = 0.009) was an independent risk factor for overall survival in HCC patients. Finally, we confirmed that si-hMex-3A could significantly inhibit HCC cell proliferation, migration, and invasion in vitro . Conclusions: HMex-3A may contribute to the progression of HCC and might be used as a novel therapeu- tic target and prognostic marker in HCC.