Poly(C)‑binding protein 2 (PCBP2) is a member of the PCBP family, and plays an important role in post‑transcriptional and translational regulation of various signaling molecules through direct binding to single‑stranded poly(C) motifs. PCBP2 has been reported to play a critical role in the development of multiple human tumors. However, whether PCBP2 participates in hepatocellular carcinoma (HCC) development remains largely elusive. Herein, we showed that PCBP2 was upregulated in human HCC tissues and cell lines. Overexpression of PCBP2 predicted significantly worsened prognosis in HCC patients, suggesting that PCBP2 may serve as a prognostic marker of HCC. In addition, we found that depletion of PCBP2 inhibited HCC cell proliferation, accompanying the increase in the cyclin‑dependent kinase inhibitor p27 level. Moreover, we found that high expression of PCBP2 may contribute to sorafenib resistance in HCC cells, involving dysregulated expression of Bax and Bcl‑2 proteins. In conclusion, our results suggest that PCBP2 may serve as a prognostic marker and potential therapeutic target of HCC.