This study is a first-time report of the development of a mercaptosuccinic acid-nickel selenide quantum dots (MSA-NiSe2 QDs)-based electrochemical aptasensor for brain natriuretic peptide (BNP) detection. Herein, novel MSA-NiSe2 QDs were synthesized by microwave irradiation. Microscopic and structural analysis revealed that the QDs are spherical with an average diameter of 2 nm. In the presence of the as-prepared QDs, an amine-modified DNA aptamer sequence was attached to a disposable sensing interface through 1-ethyl-3-(3-dimenthylaminopropyl) carbodiimide/N-hydroxysuccinimide coupling chemistries. Electroanalytical analysis revealed that the developed QDs-based electrochemical aptasensor is highly selective towards BNP and successfully detected BNP in both physiological buffer and human plasma samples with detection limits of 5.45 pg mL-1 and 31.95 pg mL-1, respectively. Moreover, the results revealed a 3-fold enhancement in the loading capacity of the BNP aptamer in the presence of MSA-NiSe2 QDs. By taking advantage of the physical and electronic properties of the novel QDs these materials can be easily adapted to other diagnostic approaches.