Abstract: OBJECTIVE To detect protein expression differences after combination-therapy on HSC-T6 and to explore antifibrotic mechanism of combination-therapy based on the protein level. METHODS HSC-T6 as target cells, cells proteins were extracted after treated by combination drug of taurine, epigallocatechin gallate (EGCG) and genistein. After equal amount of protein digested by trypsin, the iTRAQ labeled protein peptide, separated by the cation column, LC-ESI-MS/MS used to detect and identify differentially expressed proteins. The functions of proteins were analyzed by bioinformatics. RESULTS Total 727 proteins were identified by MS. Three biological replicates identified 85, 102 and 94 differentially expressed proteins respectively. The analysis manifest 52 differentially expressed proteins were identified in three biological replicates simultaneously, of which 24 differentially expressed proteins were up-regulated, 28 differentially expressed proteins were down-regulated. The differentially expressed proteins correlate with post-translational modification, transcription, recombination and signal transduction pathways. CONCLUSION Combined drug treatment with taurine, EGCG and genistein can impact HSC protein expression. The antifibrotic effects of this drug combination may be due to regulation of protein expression.