Understanding the genetic basis in animals possessing toxin could provide us significant insights into the adaptive evolution in toxin resistance. The reason of toxin resistance may refer to the mutation in sodium channels or the toxin-binding proteins. Sea snail Nassarius can accumulate tetrodotoxin (TTX) in their body and has caused serious people poisoning and death incident. However, the genetic basis of Nassarius including genetic expression and mutation has not been researched yet. Here we investigated the genetic basis from two Nassarius species (Nassarius succinctus and Nassarius variciferus) for TTX resistance with transcriptome. The genetic express pattern for both species was clearly revealed. The cellular and metabolic process, and binding and catalytic activity accounted for the top classification categories. The toxic samples generally produced more up-regulated genes than non-toxic samples. Some genes which possibly produce TTX-binding proteins were flagged. One sodium channel gene was identified from N. succinctus where one mutation cite was found as being different from all other animals included. The genetic basis of Nassarius revealed in this study would contribute to the further TTX-resistance mechanism research.