Objective To explore the changes in the expression of drug resistance genes in ovarian cancer cell lines and their biological mechanisms, and provide bioinformatics evidence for the cause and treatment of platinum resistance in ovarian cancer cell lines. Methods The A2780 platinum-resistant chemotherapy and original cell line related gene chip data set was downloaded from the Gene Expression Database (GEO) and grouped. R software was used to screen differentially expressed genes. The cluster Profiler R package was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and visualization of differential genes to find out related highly expressed gene pathways. A protein interaction network was constructed through STRING database and Cytoscape software to analyze the hub gene of the network. Cytoscape software was used to construct a protein interaction network and analyze biological processes. The CMap website was used to identify drugs related to drug resistance through differentiation of drug reactions caused by differential genes in cell lines. Results The results of multi-chipset analysis showed that the formation of platinum resistance in ovarian cancer had a small number of key changes in gene expression. There were only 32 genes with the same high expression in different research chips, and only 126 genes with low expression. The expression of genes related to the extracellular matrix signaling pathway and MAPK signaling pathway increased. The secretion of proteins related to exosomes increased. The positive regulation of cholesterol storage was enhanced. The biological processes of growth plate chondrocyte differentiation and monocyte differentiation were enhanced, indicating that the platinum resistance mechanism of ovarian cancer cells could be explored along the above two mechanisms. Six drugs such as Cycloheximide, Emetine, Cephaeline, Homoharringtonine, Verrucarin-A, Puromycin could be focused on the biological research of platinum resistance. Conclusion This study explored and analyzed the causes and treatment of platinum resistance in human ovarian cancer cells, and provided a bioinformatics theoretical basis for further research on platinum resistance in human ovarian cancer cells. [ABSTRACT FROM AUTHOR]