[Display omitted] • Cd inhibited the viability of MDA-MB-231 cells in a time- and dose-dependent manner. • Caspase-inhibitor of z-VAD reduced Cd-induced LDH release and pyroptosis. • NAC attenuated Cd-activated ROS, NLRP3 and inflammation-related genes. • MKK3/6/p38 MAPK/NF-κB pathway was activated. • Cd induced GSDME-dependent pyroptosis by activation of bax/caspase-3/GSDME pathway. Cadmium (Cd) exposure can exert an impact on carcinogenicity of breast cancer, however, the mechanism is not fully understood in triple-negative breast cancer (TNBC). We performed a TNBC MDA-MB-231 cell model and assessed the toxic effect of Cd exposure (0, 10, 20, 50, 60, 80 μM). Cd reduced cell viability in a time- and dose-dependent manner, followed by cell cycle arrest in S phase with alterations of cyclin 1A1, cyclin 1D1 and CDK2. Lactate dehydrogenase (LDH) release, apoptosis and pyroptosis were increased, which were relieved by z-VAD. Elevated ROS and NLRP3, caspase-1, IL-1β and IL-18 were detected, which was attenuated by N-acetylcysteine. Increased bax and decreased caspase-8, caspase-9 and caspase-3 were found. gasdermin E (GSDME) was activated with cleavage of GSDME-NT, which was retarded by z-VAD. Additionally, p38 MAPK signaling pathway was activated. Our data demonstrate GSDME-activated pyroptosis in Cd toxicity, implying a potential impact on TNBC. [ABSTRACT FROM AUTHOR]