Antagonism between heavy metal and selenium (Se) could significantly affect their biotoxicity, but little is known about the mechanisms underlying such microbial-mediated antagonistic processes as well as the formed products. In this work, we examined the cadmium (Cd)-Se interactions and their fates in Caenorhabditis elegans through in vivo and in vitro analysis and elucidated the machinery of Se-stimulated Cd detoxification. Although the Se introduction induced up to 3-fold higher bioaccumulation of Cd in C. elegans than the Cd-only group, the nematode viability remained at a similar level to the Cd-only group. The relatively lower level of reactive oxygen species in the Se & Cd group confirms a significantly enhanced Cd detoxification by Se. The Cd-Se interaction, mediated by multiple thiols, including glutathione and phytochelatin, resulted in the formation of less toxic cadmium selenide (CdSe)/cadmium sulfide (CdS) nanoparticles. The CdSe/CdS nanoparticles were mainly distributed in the pharynx and intestine of the nematodes, and continuously excreted from the body, which also benefitted the C. elegans survival. Our findings shed new light on the microbial-mediated Cd-Se interactions and may facilitate an improved understanding and control of Cd biotoxicity in complicated coexposure environments.