Epithelial-mesenchymal transition (EMT) has an established role in the acquisition of therapeutic resistance. Programmed cell death domain 2 (PDCD2) is involved in the progression of multiple types of cancer. However, its mechanism underlying chemoresistance in liver cancer has not been elucidated. In the present study, it was demonstrated that the sorafenib‑resistant HepG2 cell line exhibited EMT and multidrug resistance (MDR) phenotypes, and reduced expression of PDCD2, by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and Cell Counting Kit‑8. Annexin V/fluorescein isothiocyanate and cell migration assays further demonstrated that PDCD2 effectively promoted sorafenib‑induced cell apoptosis and reduced cell metastasis. Mechanistically, PDCD2 inhibited the expression of Vimentin and increased the expression of E‑cadherin in a Snail‑dependent manner by RT‑qPCR and western blot analysis. In conclusion, the present study elucidated for the first time, to the best of our knowledge, that PDCD2 sensitizes sorafenib‑resistant HepG2 cells to sorafenib by the downregulation of EMT. PDCD2 may serve as a potential therapeutic target in the treatment of sorafenib‑resistant liver cancer.