Crassostrea ariakensis naturally distributes in the intertidal and estuary region with relative low salinity ranging from 10 to 25‰. To understand the adaptive capacity of oysters to salinity stress, we conducted transcriptome analysis to investigate the metabolic pathways of salinity stress effectors in oysters from two different geographical sites, namely at salinities of 16, 23, and 30‰. We completed transcriptome sequencing of 18 samples and a total of 52,392 unigenes were obtained after assembly. Differentially expressed gene (DEG) analysis and weighted gene correlation network analysis (WGCNA) were performed using RNA-Seq transcriptomic data from eye-spot larvae at different salinities and from different populations. The results showed that at moderately high salinities (23 and 30‰), genes related to osmotic agents, oxidation-reduction processes and related regulatory networks of complex transcriptional regulation and signal transduction pathways dominated to counteract the salinity stress. Moreover, there were adaptive differences in salinity response mechanisms, especially at high salinity, in oyster larvae from different populations. These results provide a framework for understanding the interactions of multiple pathways at the system level and for elucidating the complex cellular processes involved in responding to osmotic stress and maintaining growth. Furthermore, the results facilitate further research into the biological processes underlying physiological adaptations to hypertonic stress in marine invertebrates and provide a molecular basis for our subsequent search for high salinity-tolerant populations.