We characterized and compared the venom protein profiles of Hydrophis curtus (synonyms: Lapemis hardwickii, Lapemis curtus and Hydrophis hardwickii) and Hydrophis cyanocinctus, the two representatives of medically important venomous sea snakes in Chinese waters using proteomic approaches. A total of 47 and 38 putative toxins were identified in H. curtus venom (HcuV) and H. cyanocinctus venom (HcyV), respectively, and these toxins could be grouped into 15 functional categories, mainly proteinases, phospholipases, three-finger toxins (3FTxs), lectins, protease inhibitors, ion channel inhibitors, cysteine-rich venom proteins (CRVPs) and snake venom metalloproteases (SVMPs). The constituent ratio of each toxin category varied between HcuV and HcyV with 3FTx (54% in HcuV/69% in HcyV) and PLA2 (38% in HcuV/22% in HcyV) unanimously ranked as the top two most abundant families. Both HcuV and HcyV exhibited relatively high lethality (LD₅₀ values in mice of 0.34 μg/g and 0.24 μg/g, respectively), specific PLA2 activity and hemolytic activity. On the basis of several previous reports of HcuV and HcyV collected from other areas, these findings greatly expand our understanding of geographical variation and interspecies diversity of the two sea snake venoms and can provide a scientific basis for the development of specific sea snake antivenom in the future.