Protein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, increasing evidence supports that epigenetic abnormalities PRC1 was related to multiple cancers in humans. However, pan-cancer studies of multiple human cancers are still lacking. PRC1 was overexpressed in many kinds of human tumor tissues, and the high expression of PRC1 was ralated to poor prognosis and clinical features. The results of gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analyses of the PRC1 and its co-expressed genes showed that many gene terms related to cell circle, kinesins and, regulation of cytokinesis. PPI network analysis showed PRC1 have strong interactions with KIF4A, RACGAP1, KIF20A, KIF14, PLK1, KIF20B. Moreover, PRC1 methylation and copy number variation (CNV) were shown to be strongly linked with mRNA expression in most cancer types. Additionally, we also found that the expression level of PRC1 in multiple cancer types is correlated with tumor cell immune infiltration, TMB and MSI, providing a basis for further guiding tumor immunotherapy. PRC1 may serve as a biomarker for cancer progression and poor prognosis, providing a new way of thinking for cancer treatment.