In summary, we have used bioinformatic methods to identify and validate key targets of HP for the treatment of MDD, and then investigated the mechanism of action of HP for MDD through signaling pathways and immune inflammation, identifying AKT1, MAPK1, MYC, EGF, and HSP90AA1 as key therapeutic target genes, which provide a theoretical basis for clinical treatment and drug development. This evidence concerns the gene MAPK1 and major depressive disorder.