The resistance of cancer cells to apoptosis poses a significant challenge in cancer therapy, driving the exploration of alternative cell death pathways such as pyroptosis, known for its rapid and potent effects. While initial efforts focused on chemotherapy-induced pyroptosis, concerns about systemic inflammation highlight the need for precise activation strategies. Photothermal therapy emerges as a promising non-invasive technique, minimizing pyroptosis-related side effects by targeting tumors spatially and temporally. However, accurately pinpointing tumors to avoid collateral damage remains a challenge. Thus, we utilize NIR-II fluorescence imaging to achieve precise PTT-induced pyroptosis activation in glioma. A polymer semiconductor-based PTT agent was developed with high optical stability, integrated with mesoporous silica to enhance its biocompatibility. These nanoparticles, stabilized through PEG modification and targeted with cRGD peptides, effectively induced pyroptosis in vitro. Furthermore, this design facilitated precise tumor imaging guidance and subsequent pyroptosis activation in vivo, presenting a promising strategy for glioma therapy with minimized adverse effects.