Hepatic fibrosis is defined as a pathological process, and activation of hepatic stellate cells (HSCs) is believed to be the key event of liver fibrosis. Additionally, activated HSCs may participate in the formation of the tumor microenvironment. Polaprezinc, a protector of the gastric mucosa, has been recently demonstrated to be an inhibitor of liver fibrosis in a mouse model. Proliferation and colony formation assays were performed to determine the inhibitory effects of polaprezinc on the growth of LX‑2 and hepG2 cells. A migration assay was used to evaluate the change in mobility of LX‑2 cells and quantitative polymerase chain reaction was performed to detect the expression levels of key markers of fibrosis. Finally, a gene chip assay for polaprezinc‑treated hepG2 cells was performed to evaluate the effect of polaprezinc on the hepG2 gene expression profile. The proliferation assay indicated that polaprezinc may inhibit the LX‑2 cell proliferation and the migration assays confirmed the inhibition of mobility. The expression levels of fibrotic markers such as collagen I, fibronectin and α‑smooth muscle actin were downregulated following polaprezinc treatment. The proliferation activity of polaprezinc‑treated hepG2 cells was reduced and the gene chip assay indicated that series of gene expression changes associated with cancer migration, cell skeletal organization and proliferation had occurred. In conclusion, polaprezinc treatment mayinhibit the proliferation of hepatocellular carcinoma cells and reverse liver fibrosis by deactivating HSCs. The present findings suggest that polaprezinc provides a novel treatment for patients with gastritis complicated with cirrhosis.