AIM: To explore the mRNA and pathways related to retinoblastoma (RB) genesis and development. METHODS: Microarray datasets GSE29683 (human) and GSE29685 (mouse) were downloaded from NCBI GEO database. Homologous genes between the two species were identified using WGCNA, followed by protein-protein interaction (PPI) network construction and gene enrichment analysis. Disease-related miRNAs and pathways were retrieved from miR2Disease database and Comparative Toxicogenomics Database (CTD), respectively. RESULTS: A total of 352 homologous genes were identified. Two pathways including “cell cycle” and “pathway in cancer” in CTD and enrichment analysis were identified and seven miRNAs (including hsa-miR-373, hsa-miR-34a, hsa-miR-129, hsa-miR-494, hsa-miR-503, hsa-let-7 and hsa-miR-518c) were associated with RB. miRNAs modulate “cell cycle” and “pathway in cancer” pathways via regulating 13 genes (including CCND1, CDC25C, E2F2, CDKN2D and TGFB2). CONCLUSION: These results suggest that these miRNAs play crucial roles in RB genesis through “cell cycle” and “pathway in cancer” pathways by regulating their targets including CCND1, CDC25C, E2F2 and CDKN2D.