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Objective To investigate the effect of gene expression by NSUN2 in ovarian cancer cell line A2780 by RNA-seq technology, and to provide a theoretical basis for clarifying the role of NSUN2 in the occurrence and progression of ovarian cancer. Methods Expression of NSUN2 in A2780 cells was knocked down by lentivirus-mediated RNA interference technique. The cells transfected with empty vector were used as control, and the interfering cell lines were screened for differentially expressed genes by high-throughput sequencing using RNA-seq technology. KEGG Pathway, GO analysis and GSEA enrichment analysis were used to explore the related signaling pathways and biological processes of NSUN2-regulated differential genes. Results Compared with the control cells, there were 1 642 differentially expressed genes in the A2780 cell line with NSUN2 knockdown, including 1 020 up-regulated genes and 622 down-regulated genes. Through GO analysis, KEGG Pathway and GSEA enrichment analysis, it was found that differentially expressed genes were mainly enriched in hedgehog signaling pathway and P53 signaling pathway, and were involved in viral transcription, translation initiation and regulation. Three key genes related to the P53 signaling pathway（ZMAT3, EI24 and CCND2）were screened out through further analysis of the genes related to the p53 signaling pathway. The expression results were verified by RT-qPCR and the sequencing results were consistent. Conclusion There are significant differences in gene expression profiles between A2780 sh-NSUN2 group and A2780 sh-NC group, and the differential genes are mainly concentrated in P53 signaling pathway. In ovarian cancer, NSUN2 may regulate the occurrence and development of ovarian cancer by regulating the expression of P53 signaling pathway related factors. [ABSTRACT FROM AUTHOR]