Herein, we demonstrate a one-step, scalable, solution-processed method for the growth of nickel sulfide (NiS) nanostructures using single-source precursors (SSPs) on a flexible substrate as a versatile framework for simultaneous detection of four DNA nucleobases. The as-grown NiS nanostructures exhibit a broad bandgap range and spherical morphology with high surface area and significant porosity, as confirmed by SEM, TEM, and BET surface area analysis. Consequently, the NiS/Ni-foam electrode exhibited remarkable electrochemical performance toward the oxidation of A, G, T, and C due to its large surface area, high electrode activity, and efficient electron transfer capacity. Under the optimum conditions, the electrode demonstrated selective and simultaneous detection of all four nucleobases over a wide linear range from 200 to 1000 μM for A and G, and 50 to 500 μM for T and C, with a low limit of detection of 159 μM for A, 147.6 μM for G, 16.8 μM for T, and 45.9 μM for C, along with high sensitivity of 1.2 × 10 A M for A, 6.1 × 10 A M for G, 1.2 × 10 A M for T, and 3.0 × 10 A M for C. The as-fabricated electrode revealed excellent reproducibility and stability toward nucleobase detection and demonstrated a reliable DPV response under different bending and twisting conditions. For immediate practical application, NiS/Ni-foam was utilized to quantify the concentration of all nucleobases in calf thymus and () DNA, resulting in a (G + C)/(A + T) ratio of 0.79 and 1.10, respectively. This simple, cost-effective, and flexible NiS/Ni-foam electrode paves the way for the development of non-invasive, wearable biosensors for potential applications in early disease detection.