In conclusion, this study first identified SGI‐1027 as a methuosis inducer in RCC, and SGI‐1027 combined with everolimus could exert powerful lethal effect on RCC cells by inducing LMP, providing new solution to the treatment of advanced RCC, everolimus resistance, as well as GSDME‐positive malignant tumors. The gene discussed is PDLIM7; the disease is renal cell carcinoma.