〔Abstract〕 Objective To investigate the effect of aspirin-induced Gasdermin E(GSDME) dependent pyroptosis and the related mechanism of colorectal cancer cell proliferation. Methods The colorectal cancer cells Caco2 were culturedin vitro. MTT assay was used to detect the effects of aspirin intervention with different concentrations(1.0, 2.5, 5.0, 10.0, 15.0, 20.0 mmol/L)on the proliferation activity of colorectal cancer cells. The effect of aspirin intervention on the morphology of colorectal cancer cells was observed under the microscope. Lactate dehydrogenase(LDH) release assay was used to investigate the effect of aspirin intervention on cell membrane integrity. The protein expression levels of NOD-like receptor protein(NLRP3), cysteinyl aspartate and specific proteinase 1(Caspase-1), Gasdermin E-N(GSDME-N) in colorectal cancer cells were detected by Western blot. The contents of interleukin-1β(IL-1β) and interleukin-18(IL-18) in cell supernatant after GSDME silencing were detected by ELISA. After silencing GSDME, cell morphological changes were observed under a microscope, and cell membrane integrity was observed by LDH release assay; The contents of IL-1β and IL-18 in cell supernatant were determined by ELISA after GSDME silencing. Results MTT results showed that aspirin could decrease the proliferation activity of Caco-2 in a concentration-dependent manner(P<0.01). Morphological observation and LDH experiment showed that aspirin could promote the occurrence of pyroptosis(P<0.05). Western blot showed that aspirin could increase the expression levels of NLRP3, Caspase-1, GSDME-N of pyroptosis-related pathway genes(P<0.05). ELISA showed that aspirin could significantly increase the concentration of IL-1β and IL-18 in Caco-2 cells(P<0.01). After GSDME silencing, the pyroptosis was significantly inhibited(P<0.05) and the expression of IL-1β and IL-18 decreased significantly(P<0.01). Conclusion Aspirin can inhibit the proliferation of Caco-2 by inducing the pyroptosis of GSDME-dependent cells, thus inhibiting colon cancer.