Pyruvate dehydrogenase A1 (PDHA1) is a component of the pyruvate dehydrogenase enzyme complex, which links glycolysis and the tricarboxylic acid cycle, and is important for cancer metabolism shift. PDHA1 downregulation has been revealed in several types of cancer to enhance glycolysis. However, the role of PDHA1 in gastric cancer remains largely unknown. In the present study, we found that PDHA1 was significantly downregulated in gastric cancer, and associated with poor prognosis. PDHA1 downregulation promoted gastric cancer glycolysis and cancer progression. miR‑21‑5p directly targeted PDHA1 to suppress PDHA1 expression, and promote glycolysis as well as cell proliferation in gastric cancer. Moreover, miR‑21‑5p was significantly upregulated in gastric cancer and negatively associated with PDHA1 expression in gastric cancer samples. Our results indicated that miR‑21‑5p targeted PDHA1 to regulate a metabolic switch and cancer progression in gastric cancer, and reveal the potential role of the miR‑21‑5p/PDHA1 axis in gastric cancer treatment.