The tooth is one of the ideal models for developmental study, involving in epithelial-mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time-dependent proteomic changes were investigated by healthy human molars proteomics of embryonic stages from the cap-to-early bell stage. A total of 713 differentially expressed proteins (DEPs) with five temporal expression patterns were filtered. 24 potential driver proteins of tooth development were screened by weighted gene co-expression network analysis (WGCNA) including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2 and RCC2. The hub proteins in different temporal expression patterns were extracted. And the potential cell resources and the temporal expression patterns at transcriptomic level were explored using single cell RNA-sequencing (scRNA-seq). This study provides invaluable resources for the mechanistic studies of human embryonic epithelial and mesenchymal cell differentiation and tooth development.