Cancer immunotherapies have demonstrated remarkable success; however, the majority of patients fail to respond or develop resistance, often through disruption of pathways that promote neo-antigen presentation on MHC I molecules. Here, we conducted a series of epigenetic gene-targeted CRISPR/Cas9 screens to identify epigenomic factors that limit CD8+ T cell cell-mediated anti-tumour immunity. We identified that the arginine methyltransferase PRMT1 suppressed interferon-gamma (IFNγ) induced MHC-I expression, thus dampening CD8+ T cell-mediated killing. Indeed, CRISPR/Cas9 induced knockout of PRMT1 or pharmacological targeting of type I PRMT with the clinical inhibitor GSK3368715 enhanced IFNγ-induced MHC-I expression in human and mouse tumour cells through enhanced STAT1 expression and activation, while re-introduction of PRMT1 in PRMT1 deficient cells reversed this effect. Furthermore, TCGA analysis revealed that PRMT1 expression in human melanoma is inversely correlated with expression of HLA molecules, infiltration of CD8+ T cells and overall survival. Taken together, we identify PRMT1 as a negative regulator of anti-tumour immunity, unveiling clinical PRMT1 inhibitors as novel immunotherapeutic agents or as adjuncts to existing immunotherapies where sub-optimal MHC-I expression may reduce therapeutic efficacy.