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Colorectal cancer (CRC), classified as a lethal form of cancer, substantially threatens human well-being. Cancer stem cells (CSCs) reflect subsets for cancerous cells having basic stem-cell type properties, being significantly involved in the development of chemoresistance and tumor relapsing. The aberrant TRIM27expression in various types of cancer indicates its potential involvement in cancer growth and progression. The current understanding of the TRIM27involvement in CRC remains limited. In current study indicated that TRIM27can potentially promote CSC-type phenotype of Cisplatin (DDP)-resistant CRC cells. YTHDF1recruitment onto m6A-amended TRIM27was crucial for facilitating the TRIM27translating process in DDP-resistant CRC cells. The present research proposes that TRIM27exhibits an oncogenic role by enhancing the CSC-type properties in DDP-resistant CRC viathe m6A-modified pathway. The potential therapy for combating the relapse of CRC may include TRIM27and YTHDF1, as they have been found to have significant roles in promoting CSC-type phenotypic characteristics.