〔Abstract〕 Objective To screen the mRNA core genes of naringin in the treatment of colorectal cancer(CRC) by bioinformatics analysis, and to verify the predictive effect of mRNA core genes on CRC by survival analysis. Methods The HCT116 cells of CRC were treated with DMSO solvent and naringin for 48 h and then RNA sequencing was conducted. The sequencing results were preprocessed and their differentially expressed genes were analyzed. The key lncRNAs were screened from differentially expressed genes, and the corresponding lncRNA-miRNA-mRNA regulatory network was established. With gene ontology(GO) analysis, Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and Protein-Protein Interaction(PPI) network analysis, the core mRNAs were obtained and verified by survival analysis method. Results Ultimately, 197 differentially expressed lncRNAs, 128 differentially expressed miRNAs and 1 938 differentially expressed mRNAs were screened. Based on lncRNA-miRNA-mRNA regulatory network, 5 key lncRNAs and 117 key mRNAs were screened. The results of GO analysis and KEGG pathway analysis showed that they were mainly enriched in the functions and pathways closely related to CRC. In the end, 6 mRNA core genes were obtained by PPI network analysis, and 3 core mRNAs(FOS,CCND2,MXD1) were gained by survival analysis, which closely resembled CRC. Conclusion The molecular mechanism of naringin in the treatment of CRC is analyzed by means of bioinformatics, 3 core mRNAs with significant differences are screened out and they all have an important impact on the prognoses of patients, and the study will provide new ideas for the diagnosis, treatment and prognosis of CRC.