Background: Aquatic plants and freshwater snails are important natural food sources of Eriocheir sinensis, which play important roles in the growth and development of E. sinensis. However, research on how aquatic plants and freshwater snails affect the growth and development of E. sinensis remains scant.Methods: The effects of the two kinds of natural food sources on the growth and development of E. sinensis were studied by determining the hepatopancreatic proteomes of three groups, namely, E. sinensis fed with aquatic plants combined with freshwater snails (group A), E. sinensis fed with aquatic plants only (group B), and E. sinensis fed with freshwater snails only (group C), using tandem mass tag technology.Results: A total of 110 differentially expressed proteins between groups A and B were identified, among which 78 were up-regulated and 32 were down-regulated in group A. Meanwhile, nine proteins were up-regulated, and 14 proteins were down-regulated in group A relative to those in group C. The proteins related to molting and growth such as cryptocyanin and cuticle protein CBM were up-regulated in group A compared with group B. The immunity-related proteins, such as mannosyl-oligosaccharide glucosidase and glutathione peroxidase, that were differentially expressed between groups A and C, were up-regulated in group A.Conclusion: The results indicated that freshwater snails might promote the growth and development of E. sinensis to a certain extent, and aquatic plants might play an important role in the immunity of E. sinensis. Our study provides a theoretical basis for the practice of “providing aquatic plants and freshwater snails” in the ecological culture of E. sinensis.