Objective To investigate the potential pathogenic mechanisms shared by Parkinson's disease (PD) and major depressive disorder (MDD) due to the fact that depressive symptoms are common non-motor symptoms of PD.Methods Text mining and transcriptomic data analysis were used to find the pathogenic mechanisms shared by PD and MDD.Results Text mining found that 63.8% of MDD genes and 32% of PD genes were shared genes, and the two had 438 shared biological processes; the transcriptomic data analysis screened out 10 significantly differential genes[myosin IF (MYO1F), leukocyte immunoglobulin-like receptor A2 (LILRA2), adenylate cyclase-activating polypeptide 1 (ADCYAP1), myosin light chain kinase 2 (MYLK2), calsyntenin 2 (CLSTN2), calcium/calmodulin-dependent protein kinase type IV (CAMK4), proprotein convertase subtilisin/kexin type 1 (PCSK1), transient receptor potential cation channel, subfamily C, member 5 (TRPC5), sodium/glucose cotransporter 1 (SLC5A1), tyrosinase-related protein 1 (TYPR1)] (P<0.01); the gene set enrichment analysis revealed 14 biological processes, 6 cell components, 10 molecular functions, and 3 identical Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways (P<0.05), all of which were shared by PD and MDD. Four key genes (MYO1F, CAMK4, PCSK1, and TRPC5) shared by PD and MDD were screened out by constructing protein-protein interaction networks (PPINs), and the analysis of the modules from the PPINs suggested that the key modules shared common biological processes.Conclusions PD and MDD share common pathogenic genes and pathways, which provides a theoretical basis for coincidence of PD with MDD.