To elucidate the mechanisms underlying the antitumor effects of the nanoparticle co‐delivery system and its regulation of the SCLC immune microenvironment, we treated NCI‐H446 and DMS114 cells with PRL@RBCM‐cRGD and siPFKFB4/PRLPTX@RBCM‐cRGD, followed by transcriptomic analysis. This evidence concerns the gene PRL and small cell lung carcinoma.