Rice serves as the main food source in many regions of the world. However, rice production is impacted by abiotic stress including drought, salt, temperature shifts, submersion, etc. Some rice accessions have a genetic potential to withstand in such stress conditions. Thus, identification and characterization of genes that are responsible to endure abiotic stress conditions are critical for developing new rice varieties with improved characteristics. In this respect, we studied the protein–protein interaction (PPI) network in abiotic stress-tolerant genes of rice cultivars. We explored various rice genome databases to retrieve abiotic stress-tolerant genes for this purpose. In total, 7984 genes were collected from different databases; out of these, 1408 were successfully mapped in PPI network of STRING. Subsequently, the network topology, hub protein identification, sub-network generation and functional enrichment analysis were performed using different plug-ins implemented in Cytoscape 3.9.0. We identified 17 key genes (MPK5, WRKY24, WRKY28, P5CS, DREB2A, MYB2, CLPB1, HSP81-2, HSP90, MCM2, NHX2, APX1, NYC1, CDKB1-1, CDKB2-1, ORR5 and HK4) after analysis of network using cytoHubba and MCODE tools. These identified key genes were effectively classified across diverse biological processes, encompassing hydrogen peroxide detoxification, cellular components like transport systems and molecular functions such as transcriptional activation and repression. Further, among identified key genes DREB2A, APX1 and NHX2, and MYB2, WRKY28 and WRKY24 were found to be upregulated and downregulated, respectively, in rice cultivars for different stress conditions (cold, salt and drought) in publicly available expression datasets. This information enables researchers and breeders for the development of novel abiotic stress-tolerant rice varieties.