MicroRNAs (miRNAs) are a family of small, non‑coding RNA molecules that are highly conserved across species and function as regulators of gene expression. In the present study, we revealed that miR-138 expression was at a low level while sirtuin type 1 (Sirt1) mRNA expression was at high level in hepatocellular carcinoma tissues and cell lines by using real-time PCR and western blot assays, and the functions of miR-138 were achieved via targeting of Sirt1 using luciferase reporter gene vector and RNA immunoprecipitation assays. Overexpression of miR-138 attenuated Sirt1 expression and inhibited cell proliferation by using CCK-8 and BrdU assays. The inhibitory effect of miR-138 could be partially restored by forced expression of Sirt1 in cells. Our data revealed a crucial role and mechanism of miR-138 in the regulation of hepatocellular carcinoma cell growth via the miR-138/Sirt1 axis, and miR-138 could be an important potential target for the clinical management of hepatocellular carcinoma in the future.