Abstract: Objective To study the role of ubiquitin-conjugating enzyme 9 ( UBC9) in the pyroptosis of homocysteine-induced macrophages mediated by small ubiquitin-like modifier (SUMO) modification. Methods First, the effects of homocysteine at different concentrations (0 μmol / L, 50 μmol / L, 100 μmol / L, 150 μmol / L and 200 μmol / L) on the viability and pyrodeath of mouse macrophages (RAW264. 7) were detected by CCK-8 and Western blot. Western blot was used to detect the expression levels of UBC9, SUMO-1, and the inflammatory cytokine IL-1β in different groups of cells. qRT-PCR was used to detect the mRNA expression of UBC9 before and after RNA interference and the expression of UBC9, pyrogen-related protein, and SUMO-1 after RNA interference. Results After stimulation with 100 μmol / L homocysteine, the effect of macrophage activity was minimal, and NLRP3 and Caspase-1 were the proteins with the most obvious increase in expression (P<0. 05). Compared with the Control group, the Hcy group’ s expression of IL-1β and SUMO-1 was increased (P<0. 01). Compared with the Control group, the Hcy group’ s UBC9 protein and mRNA levels were increased (P<0. 05). The expression of NLRP3, Caspase-1, IL-1β, UBC9, and SUMO-1 was decreased in the siUBC9 + Hcy group compared with the si-NC+Hcy group (P<0. 01). Conclusions Homocysteine induces pyroptosis in macrophages, and its mechanism of action is related to the up-regulation of UBC9 to induce SUMO modification.