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Malaria is the most pernicious parasitic infection, and Plasmodium falciparum is the most virulent species with substantial morbidity and mortality worldwide. The present in silico investigation was performed to reveal the biophysical characteristics and immunogenic epitopes of the 14 blood-stage proteins of the P. falciparum using comprehensive immunoinformatics approaches. For this aim, various web servers were employed to predict subcellular localization, antigenicity, allergenicity, solubility, physicochemical properties, posttranslational modification sites (PTMs), the presence of signal peptide, and transmembrane domains. Moreover, structural analysis for secondary and 3D model predictions were performed for all and stable proteins, respectively. Finally, human helper T lymphocyte (HTL) epitopes were predicted using HLA reference set of IEDB server and screened in terms of antigenicity, allergenicity, and IFN-γ induction as well as population coverage. Also, a multiserver B-cell epitope prediction was done with subsequent screening for antigenicity, allergenicity, and solubility. Altogether, these proteins showed appropriate antigenicity, abundant PTMs, and many B-cell and HTL epitopes, which could be directed for future vaccination studies in the context of multiepitope vaccine design.