Objective To study the role of ubiquitin Conjugating Enzyme 9 (UBC9) in the pyrodeath of homocysteine-induced macrophages mediated by SUMO modification. Methods Firstly, The effects of homocysteine at different concentrations (0μmol/L, 50μmol/L, 100μmol/L, 150μmol/L, 200μmol/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-modified protein SUMO-1 and inflammatory cytokine IL-1β in different groups of cells. qRT-PCR was used to detect the mRNA expression of UBC9 before and after interference, and to detect the expression of UBC9, pyrogen-related protein and SUCO-1 after interference.Results After stimulation with 100μmol/L Hcy, the activity of macrophages was not affected, and the expressions of NLRP3 and caspase-1 were the most obvious (P < 0.05).Compared with Control group, the expression levels of and IL-1β were increased in Hcy group (P < 0.01), and the expression of SUMO-1 was increased (P < 0.01). Compared with Control group, UBC9 protein level and mRNA level in Hcy group were increased (P < 0.05). After transfection with si-UBC9, the expressions of NLRP3, caspase-1, IL-1β, UBC9 and SUMO-1 in si-UBC9+Hcy group were decreased compared with si-NC+Hcy group (P < 0.01). Conclusion Hyperhomocysteamine (Hcy) induces pyrodeath in macrophages, and its mechanism is related to the up-regulation of ubiquitin binding enzyme 9 to SUMO modification.