Aim To investigate the effect of succinate on pyroptosis of human umbilical vein endothelial cells (HUVEC) and its regulatory mechanism. Methods HUVECs were treated with succinate analogue diethyl succinate (DS) for 24 h, and the content of succinate was detected by colorimetry. Western blot was used to detect the expressions of pyroptosis-related protein cysteinyl aspartate specific proteinase 1 (Caspase-1), interleukin-1β (IL-1β), IL-18, NOD-like receptor protein 3 (NLRP3), gasdermin D N termine (GSDMD-N). The effects of succinate on ATP and reactive oxygen species (ROS) production of HUVEC were detected by ATP assay kit and ROS fluorescent probe. ROS scavenger N-acetylcysteine (NAC) was used to observe the role of ROS in HUVEC pyroptosis induced by succinate. Dimethyl malonate (DMM), a succinate oxidation inhibitor, was used to detect the effect of succinate oxidative metabolism on ROS production. Results DS promoted the accumulation of succinate in HUVEC, up-regulated the expressions of pyroptosis-related proteins Caspase-1, IL-1β, IL-18, GSDMD-N and NLRP3, inhibited ATP production and up-regulated ROS production. NAC inhibited the production of ROS induced by succinate and down-regulated the expressions of above pyroptosis-related proteins. DMM down-regulated succinate-induced ROS production and HUVEC pyroptosis. Conclusion Succinate up-regulates ROS production through oxidative metabolism, thus promoting HUVEC pyroptosis.