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This paper investigates the numerical analysis of a highly performed surface plasmon resonance (SPRE)-based sensor employing a hybrid structure of SrTiO3 (STO) and graphene for rapid detection of malaria. The investigation is performed using the angular interrogation technique and transfer matrix method. The SPRE device has a glass prism, silver (Ag), STO, graphene, affinity layer and sensing medium (SGM). Four coupling prisms are examined and we found the prism N-FK51A corresponds to the highest sensitivity. The sensitivity of the structure N-FK51A/Ag/STO/graphene/affinity layer/SGM is found to be 205.405, 222.222 and [Formula: see text]/RIU for Schizont, Trophozoite and Ring malaria stages. The layer thicknesses are then optimized and it is found that the proposed SPRE sensor can achieve a sensitivity of 278.378, 227.027 and [Formula: see text]/RIU for Schizont, Trophozoite and Ring malaria stages with 30 nm (silver), 1[Formula: see text]nm (STO), mono-sheet of graphene and 5[Formula: see text]nm of the affinity layer. These findings demonstrate that the proposed method and structure can be used efficiently for biomedical applications.