Objective: The study aimed to provide novel insight into the mechanism of platinum resistance of ovarian cancer. Materials and Methods: RNA-seq data ERP000710 were obtained from Gene Expression Omnibus database, including specimens from six platinum sensitive samples and six platinum tolerance samples. The author analyzed the data of the 12 samples as a whole because of the low flux sequencing. Single nucleotide polymorphisms (SNPs) were identified between platinum-sensitive and platinum-tolerant samples using VARSCAN, followed by functional prediction of the SNPs. After processed by Btrim software, the data were subjected to Cuffdiff for the identification of differentially expressed genes (DEGs), followed by function and pathway enrichment analysis. In addition, VARSCAN software was used to detect the specific mutations in platinum tolerance samples, combined with functional prediction of mutations. Results: The author obtained 38 new SNPs after excluding 22 SNP from dbSNP database and 1000 Genomes Project and found ESRP1, LDHA, DDX5, and HEXA were associated with platinum resistance of ovarian cancer. Totally, 290 upregulated and 157 downregulated genes were selected. Biological processes such as immune response, inflammatory response, and response to wounding and pathways such as cell adhesion molecules, calcium signaling, and NOD-like receptor signaling pathways were enriched with upregulated genes. Cell-cell signaling, cell morphogenesis, and basal cell carcinoma pathway were related to downregulated genes. Conclusion: Based on high-throughput RNA-seq data and confluence analysis of multiple omics, the author explored the biological mechanisms on platinum tolerance of ovarian cancer, which may provide new ideas and methods for further research.