Nasopharyngeal carcinoma (NPC) is a common disease with high prevalence worldwide, affecting hundreds of thousands of patients every year. Although its progress can be inhibited by concurrent chemoradiotherapy and platinum-based agents, there is also a need for novel drugs to treat NPC. The present study identified tanshinone IIA as a potent drug that could suppress the proliferation of HK1 cells by enhancing pyroptosis via regulation of the miR-125b/foxp3/caspase-1 signaling pathway. Firstly, the effects of tanshinone IIA on HK1 cells were assessed and it was confirmed that treatment with tanshinone IIA significantly decreased the proliferation of HK1 cells, with increased activity of caspase-3 and caspase-9. Then, the pyroptosis levels after tanshinone IIA administration were detected. The results showed that tanshinone IIA enhanced pyroptosis in a dose-dependent manner. Furthermore, the mechanism underlying the effects of tanshinone IIA on HK1 cells were explored. It was found that transfection with a microRNA (miR)-125b agomir and a small interfering RNA (si)-foxp3 plasmid reversed the inhibitory effect induced by tanshinone IIA, accompanied by an increase in reactive oxygen species levels and lactate dehydrogenase release, indicating a critical role of miR-125b/foxp3 signaling in pyroptosis in HK1 cells. In conclusion, the present study demonstrates that tanshinone IIA enhances pyroptosis and inhibits the proliferation of HK1 cells by modulating miR-125b/foxp3/caspase-1/GSDMD signaling. It is the first study to reveal the inhibitory effect of tanshinone IIA on HK1 cells and to demonstrate the critical role of miR-125b/foxp3 signaling in mediating these effects, providing robust evidence for the treatment of NPC.