Our pan-cancer analysis establishes HMCN1 as a critical oncogenic ECM component that is frequently upregulated across cancers, with its high expression serving as a potential prognostic biomarker that is associated with poorer survival in a linear manner. Genomic analyses revealed that HMCN1 mutations are predominantly missense and positively correlate with genomic instability. This evidence concerns the gene HMCN1 and cancer.