Through PPI network analysis of these 23 target genes, we confirmed that MLKL, IL1B, CASP8, CASP1, RIPK1, TLR4, NLRP3, RIPK3, TNF, STAT3 as the potential target genes of Xiaoyaosan in the treatment of depression, among which the MCC score of MLKL was the highest. Here, CASP8 is linked to major depressive disorder.