Apocynum venetum L. is a precious wild plant germplasm resource in China, which has important medicinal value, ecological value and economic value. Although A. venetum is a plant with strong salt tolerance, the wild population has gradually decreased with the destruction of habitat and the increase of soil salinization. To explore the mechanism of salt tolerance of A. venetum is of great significance for the protection and utilization of wild germplasm resources. In this study, TMT technology was used to conduct quantitative proteomic research on A. venetum under salt stress, and different proteins at different time points were found by Venn analysis. The 11 common differential proteins were mainly concentrated in protein-FAD linkage, negative regulation of transporter activity, negative regulation of ion transmembrane transporter activity, negative regulation of anion transmembrane transport, negative regulation of anion channel activity, and thiazole metabolism. The interaction analysis of differential protein networks showed that ribosomal proteins were the main proteins obtained by the interaction of differential protein networks at different stress times, among which the ribosomal protein L2-2 (TRINITY_DN13265_c0_g1_i1_9) was the core protein in the differential proteins at 12 h and 24 h under stress. The results indicated that ribosomal proteins played an important role in the response of A. venetum to salt stress. In this study, the key proteins of A. venetum in response to salt stress were screened, the molecular resources related to A. venetum salt stress response were expanded, and the theoretical basis was provided for the discovery and utilization of natural resistance germplasm of A. venetum.