It has been revealed by our previous proteomic study that the expression profile is different between well‑differentiated and poorly differentiated hepatocellular carcinoma (HCC). Among those differently expressed proteins, peroxiredoxin2 (PRDX2) was our protein of interest. The present study aimed to further investigate the value of PRDX2 as a prognostic factor in HCC. Tissue microarrays were used to investigate the expression difference between HCC tissues and their adjacent normal liver tissues. The expression of PRDX2 at both mRNA and protein levels was examined by q‑RT‑PCR, western blotting and immunohistochemical assessment in HCC tissues and cell line HCCLM3. Silencing of PRDX2 in HCCLM3 was achieved usingpGMLV‑SC1 lentiviral vectors. Cell Counting Kit‑8 (CCK‑8) and Transwell migration assays were used to assess cell proliferation and migration, respectively. Categorical variables were assessed using the Chi‑square test, and ordinal variables were examined using the Mann‑Whitney U test. The difference of continuous variables between groups were compared with t‑tests. The Kaplan‑Meier method was used to calculate the overall survival (OS) and disease‑free survival (DFS) of patients, and the log‑rank test was used to analyze the differences between groups. The results revealed that the expression of PRDX2 was decreased at both the mRNA and protein levels in an HCC cell line compared to that of a normal human liver cell line. PRDX2 protein expression levels were significantly downregulated in HCC tissues and were positively linked to overall survival (OS) and disease‑free survival (DFS) of HCC patients. Patients with high PRDX2 expression levels had longer OS and DFS times than those with lower PRDX2 expression. Silencing of PRDX2 in the HCC cell line HCCLM3 promoted cancer cell proliferation and migration. Our findings indicated that PRDX2 may play an important role in HCC development; PRDX2 may serve as a useful prognostic factor and a therapeutic target.