Understanding the genetic basis of tetrodotoxin (TTX) accumulation and resistance in animals could provide us significant insights into adaptive evolution in ecological communities. It has been reported that TTX resistance is possibly due to gene mutation in sodium channels. Eating sea snail Nassarius has caused serious people poisoning and death incident due to tetrodotoxin (TTX) accumulation in their body. Here we conducted transcriptome analysis for both toxic and non-toxic communities in two Nassarius species (Nassarius succinctus and Nassarius variciferus) to reveal their genetic patterns of TTX accumulation and resistance. For genetic expression, the cellular and metabolic process, and binding and catalytic activity accounted for the top classification categories for both species. The toxic communities generally produced more up-regulated genes than non-toxic communities. The mostly different expression genes among toxic and non-toxic communities mainly included heat shock protein 83-like, cytochrome c oxidase subunit, WAS protein family member 2, delta-aminolevulinic acid dehydratase, protein transport protein Sec24D isoform X2 and so on, some of which referred to detoxification. In mutation level, the sodium channel gene of N. succinctus had one amino acid “L” that is different from that of other animals. The transcriptome analysis of both toxic and nontoxic communities in two Nassarius species provided important genetic basis for adaptive evolution research of TTX accumulation and resistance.