The Chinese mitten crab (Eriocheir sinensis) is widely distributed along eastern China, where northern and southern populations may have evolved different environmental adaptation mechanisms. DNA methylation, as an important epigenetic modification, plays a key regulatory role in environmental adaptation. In this study, muscle and hepatopancreas tissues from E. sinensis populations of the Liaohe River (LH) and Beilunhe River (BLH) were subjected to integrated RNA-seq and whole-genome bisulfite sequencing (WGBS) analyses, generating 12 mRNA libraries and 12 DNA methylation libraries. RNA-seq analysis identified 622 and 783 differentially expressed genes (DEGs) in muscle and the hepatopancreas, respectively, in the LH group compared with the BLH group, with downregulated genes accounting for a larger proportion. WGBS analysis showed that genome-wide DNA methylation in E. sinensis was predominantly in the CG context, with the highest methylation levels observed in gene body regions. A total of 972 and 991 differentially methylated regions (DMRs) were identified in muscle and the hepatopancreas, respectively. Integrated analysis further identified 10 differentially methylated and expressed genes (DMEGs) in muscle and 26 DMEGs in the hepatopancreas. Notably, no single fixed pattern was observed between methylation changes and gene expression changes in either tissue. These findings suggest that DNA methylation may participate in environmental adaptation in northern and southern populations of E. sinensis by modulating gene expression. Our results highlight the important role of epigenetic regulation in the evolutionary adaptation of crustaceans to different environments and provide a theoretical basis for the development of environment-associated molecular markers and the evaluation of adaptive germplasm resources.