N6-methyladenosine (m⁶A) modification is the most abundant and dynamic RNA modification that critically influences transcript fate post-transcriptionally. This study investigated the role of m⁶A RNA modification in regulating the response to cisplatin (CP) treatment in HeLa cells. The status of core m⁶A modulators following CP exposure was examined, followed by a transcriptome-wide analysis of m⁶A methylation. The findings revealed significant alterations in the m⁶A RNA methylation landscape by possible effects of changes in the expression of key m⁶A writer proteins, particularly METTL14. METTL14 depletion increased CP sensitivity, significantly elevating RNA levels of cell-death-related genes at the 72nd and 96th hrs after siRNA transfection. Genes such as ATF3, ATF5, DUSP6, and PEA15 displayed consistent expression patterns, while TP73, BMF, DAPK1, and DAB2IP exhibited opposite mRNA levels compared to those identified in CP RNA-seq data. These findings suggest that METTL14-directed methylation plays a crucial role in the mRNA regulation of these genes. Furthermore, YTHDF2 was found to regulate mRNA abundance of candidates through mRNA decay, with enriched binding to pro-apoptotic genes (TP73, DAPK1, ATF3, BMF, GADD34, ATF3, DUSP6) in control cells rather than CP-treated cells. This indicates that these genes might be subject to YTHDF2-mediated post-transcriptional regulation. This study highlights the dynamic nature of m⁶A modification in response to CP treatment. It underscores the significant role of METTL14 in modulating transcript fate, providing a foundation for future research into therapeutic strategies targeting m⁶A regulatory pathways in cancer treatment.