One major topic in colorectal cancer (CRC) research is the role of immune cells against cancer cells. The association of single-nucleotide polymorphisms (SNPs) and polygenic risk scores (PRS) with CRC was examined and their functional properties were identified using a gene-gene interaction network. 960 CRC patients at Seoul National University Hospital (SNUH, discovery) and 6,627 CRC patients at Chonnam National University Hospital (CNNUH, validation) were enrolled. SNPs were genotyped using the Korean Biobank Array. 2,729 immune-related genes were selected from the Ensembl, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes, and 37,398 SNPs were mapped. PRS were categorized into tertiles. Cox proportional hazard models were fitted for overall survival (OS) and progression-free survival (PFS). A gene-gene interaction network was analyzed. Among CRC patients from SNUH, 154 (16.0%) died, while 245 (25.5%) had progression. In CNNUH, 3,537 (53.4%) died. For OS, the most significant association was observed for rs117322760 (8q23.1, PKHD1L1, hazard ratio (HR) = 4.58, p-value = 1.40 × 10