This study highlights the epigenetic role of PRMT5 in regulating Dickkopf family protein 1 (DKK1), possibility through symmetrical dimethylation of H3R8. Moreover, inhibition of DKK1 or inhibition of PRMT5 with the inhibitor CMP5, combined with DOX, resulted in increased anti-tumour effects in KRAS mutant CRC cells, but not KRAS wild type cells. This evidence concerns the gene DKK1 and neoplasm.