Taxilli Herba (TH) is famous for its semi-parasitic feature, with hundreds of host species. The molecular mechanisms governing the accumulation of bioactive constituents in TH from different hosts have yet to be completely understood. The purpose of this study was to investigate the differences in synthesis and accumulation of bioactive constituents in TH from Morus alba L. and Liquidambar formosana Hance. The proteome of TH from two hosts were compared, and proteins were identified using tandem mass tag (TMT) technology. Sixteen bioactive constituents were quantitatively determined and analyzed in conjunction with the results of proteomics. A total of 5681 proteins were detected, of which 259 were significantly up-regulated and 274 significantly down-regulated in expression levels. Differentially expressed proteins (DEPs) were shown to be mostly engaged in cellular process and metabolic process by GO analysis. DEPs were considerably abundant in amino acid metabolic pathways, according to KEGG pathway analysis. The changes in the contents of 16 bioactive constituents were mostly compatible with the expression patterns of relevant structural proteins. The results of this study will provide basic information for the role of protein in the secondary metabolism biosynthesis pathway and the molecular mechanism of the quality formation of TH.