Update publication information. Normal epididymis development is the basis of male reproduction, and epididymis is a crucial site where sperm maturation occurs. Although epididymis has been studied through multiple omics methods, combined omics has not been used to present the differential genes in the epididymal cauda of yaks before and after sexual maturity. We here provided the landscape maps of differential genes and proteins obtained through RNA-seq and proteomics technology, and searched for potential key genes, including TGFBI, COL1A1, COL1A2, COL3A1, COL12A1, SULT2B1, KRT19, and NPC2, through integration analysis. In separate and combined enrichment analyses, genes mainly related to cell growth, differentiation and adhesion, sperm maturation, and immune defense were differentially expressed. The involved pathways included extracellular matrix (ECM)–receptor interaction, protein differentiation and absorption, lysosomes, and estrogen signaling pathway. When the sequencing results were verified through qRT-PCR and 4D-PRM, they were found to be consistent. In addition, after the key genes were identified, abnormal expression of these genes was found to possibly cause the retardation of cauda epididymis development and abnormal sperm function in yaks. In conclusion, we provide useful clues for the development of epididymal cauda of yak, sperm maturation, and screening of key genes involved in reproductive regulation of male yak through separate and combined analyses.