Protocadherin10 (PCDH10), a member of the non‑clustered protocadherin (PCDH) family, functions as a tumor-suppressor gene in many cancers. Previous studies have demonstrated that the expression of PCDH10 was noticeably downregulated in the tissue and cells of hepatocellular carcinoma (HCC), when compared to those in normal liver tissue. The decreased PCDH10 expression in HCC was correlated with the aberrant methylation status of PCDH10 promoter. However, the biological functions and molecular mechanism of PCDH10 in HCC have yet to be elucidated. The aim of the present study was to identify the biological function and mechanisms of PCDH10 in HCC. Quantitative real-time polymerase chain reaction was used to detect the expression of PCDH10 in HCC cells with decreased expression of PCDH10 which were transfected with plasmid pcDNA3.1-PCDH10 or pcDNA3.1-vector using Lipofectamine 2000. The biological effects of PCDH10 in HCC cells were detected by CCK-8, colony formation and flow cytometric assays. Western blot and co-immunoprecipitation (Co-IP) assays were performed to explore the mechanism of PCDH10 in HCC cells. PCDH10 expression was downregulated in the HCC cells (HepG2, HuH7, HuH1, and SNU387) when compared to the normal liver cells (L02). Upregulation of PCDH10 inhibited cell proliferation and induced cell apoptosis in the HCC cells. More importantly, we revealed that PCDH10 inhibited the PI3K/Akt signaling pathway thus carrying out its suppressive function in HCC. This study provides insights into the tumorigenesis and progression of HCC, and puts forward the novel hypothesis that PCDH10 could be a new biomarker for HCC, or that combined with other molecular markers could increase the specificity and sensitivity of diagnostic tests for HCC. Restoration of PCDH10 could be a valuable therapeutic target for HCC.