Cucurbitacin B (CuB), a bioactive component from muskmelon pedicel, could bound the TLR4 to activate the NLRP3 inflammasome and separate of N‐ and C‐terminals of GSDMD to induce TLR4/NLRP3/GSDMD‐dependent pyroptosis for antitumor therapy of A549 NSCLC.251. Here, TLR4 is linked to non-small cell lung carcinoma.