Long term low-dose benzene exposure lead to the inhibition of hematopoiesis. However, the underlying mechanisms of benzene related hypocytosis remained poorly defined, especially mediated by the early effector molecule. Here, we first found that several pyroptotic classic genes such as Casp1, 4, 5, IL1β, and IL-18 represented the occurrence of cell pyroptosis were up-regulated and represented dose-dependent differential expression in controls, benzene-exposure workers, and chronic benzene poisoning workers. Meanwhile, the expression of pyroptosis classical genes including Caspase 1 (Casp1) and interleukin 1beta (IL1β) were significantly up-regulated in low-dose benzene-exposed workers accompanied with potent proinflammatory IL1β elevated which showed a negative correlation trend with WBC, NEUT, LYMPH, and PLT. In vitro studies showed that 1,4-Benzoquinone (1,4-BQ), one of important benzene metabolites, induced AHH-1 cells pyroptosis, a novel proinflammatory form of cell death, through activating Aim2/ Casp1 pathway accompanied with the increased expression of Gasdermin D (GSDMD). Among them the up-regulation of TET2 was found both elevated in low benzeneexposed workers and the AHH-1 cells treated with 1,4-BQ, meanwhile, TET2 was positively correlated with IL1β which indicted TET2 potentially played an important role in cell pyroptosis death. Further, we verified that cell pyroptosis death caused by 1,4-BQ could be ameliorated in vitro by RNAi or pretreatment with DMOG, the inhibitor of TET2. In conclusion, our results demonstrated that exposure to benzene can trigger cell pyroptosis death via TET2 directly regulating Aim2/Casp1 signaling pathway to cause hematotoxicity. This work provides novel proof for the study of toxic effects and risk assessment of benzene. Funding Statement: This research was supported by the National Natural Science Foundation of China (81773397, 81472957), the Support Project of High–level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan (CIT&TCD 20170323), Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ201810025032). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board of Capital Medical University, and informed consent was obtained from all subjects prior to their recruitment into the study.