BACKGROUND: Incidences of resistance to current drugs by Plasmodium is increasing, hence, it is necessary to investigate and explore new drug targets to combat malarial disease.OBJECTIVE: Analysis of the transcriptome sequence information to characterize hub genes and their nonsynonymous single nucleotide polymorphisms (nsSNPs) to derive therapeutic objectives for Plasmodium falciparum.MATERIALS AND METHODS: Differentially expressed genes between Ring and other stages of P. falciparum were identified using Cufflinks tool. Using DAVID and KAAS programs, the gene ontology and pathway analysis were performed. The networks of protein‑protein interaction (PPI) were developed by Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape, and the node degree in the network was calculated by using Network Analyzer, and MCODE plugins of Cytoscape. SIFT, PROVEAN, and PredictSNP programs were used to study the genetic variations, which affect protein functions.RESULTS: Alist of 4196 nonredundant genes was used for functional annotation cluster analysis, and 8 significant hub genes have been picked from the PPI network using MCODE plugins of Cytoscape. Various nsSNPs were identified in these 8 hub genes and were investigated both for its native and mutant stage for solvent accessibility and alteration in secondary structure protein residues.CONCLUSION: Hub genes identified in this study serve as potential targets to develop therapy to suppress the pathogenic action of P.falciprum through experimental techniques