α‑Fetoprotein (AFP)‑producing gastric cancer (AFPGC) is recognized as one of the most aggressive tumors with subsequent poor prognosis compared with common gastric cancer (GC) subtypes. However, the molecular mechanism remains to be elucidated. We previously identified that miR‑122‑5p could be a useful biomarker in AFPGC patients. We examined herein the biological function of miR‑122‑5p and the molecular mechanism underlying tumor progression in AFPGC. We used the AFPGC cell line (FU97) and miR‑122‑5p inhibitor to examine the function of miR‑122‑5p. Moreover, we investigated the possible targets of miR‑122‑5p. The expression level of miR‑122‑5p was significantly increased in the FU97 cell line than in common GC cell lines. Also, suppression of miR‑122‑5p significantly reduced AFP levels and proliferation in AFPGC through an induction of apoptosis. Western blotting revealed that the expression of anti‑apoptotic protein (Bcl‑2) was decreased and that of pro‑apoptotic protein (caspase‑3) was increased in miR‑122‑5p suppression of FU97. Moreover, we revealed that FOXO3 was an important target of miR‑122‑5p in AFPGC, which inhibited apoptosis and subsequently manifested aggressiveness. In conclusion, miR‑122‑5p inhibited apoptosis and facilitated tumor progression by targeting FOXO3 in AFPGC, which indicates the possibility of miR‑122‑5p as a potential therapeutic target in AFPGC.