Arsenolipid (AsL) is a complex lipid-soluble organic arsenic compound, which is usually found in marine organisms. Among them, arsenic-containing hydrocarbons (AsHCs) are a common type. At present, the toxic effects of different AsHCs have not been elucidated due to their different hydrocarbon chain lengths and large numbers. A model Caenorhabditis elegans (C.elegans) was used to study the reproductive toxicity and mechanism of AsHC 332, AsHC 346 and AsHC 360, which are commonly found in seafood. The results showed that three different molecular weights of AsLs reduced the number of offspring and gonadal area of C.elegans, prolonged the generation time. Meanwhile, the three AsLs regulated the expression levels of oxidative stress genes (isp-1, mev-1, sod-3, gas-1), resulting in changes in the expression of apoptosis-related genes (ced-3, ced-4, ced-9) and DNA damage-related genes (hus-1, clk-2, cep-1 and egl-1). In addition, the mechanism of arsenolipid-induced nematode reproductive toxicity was further elucidated through the HUS-1-CEP-1-EGL-1-CED-9-CED-4-CED-3 signaling pathway. Therefore, our results suggest that AsHC 332 is more exposed to reproductive toxicity than AsHC 346 and AsHC 360, which is related to changes in physicochemical properties and DNA damage-induced germ cell apoptosis.