Abstract: The chemical stability, good biocompatibility and high drug loading capacity of zinc oxide nanoparticles (ZnO NPs) and their biomedical potentials make them promising candidates for drug delivery. The aim of this study is to develop and assess a simple procedure for capping and surface functionalization of ZnO NPs by N−acetyl−L−cysteine (NAC) for anticancer curcumin (Cur) delivery. NAC capped ZnO NPs (ZnO−NAC NPs) have been successfully made by using ZnCl₂ and NaOH in the presence of NAC. Curcumin has been conjugated covalently to the surface of as−synthesized ZnO−NAC NPs. To characterize the synthesized conjugate product (ZnO−NAC−Cur NPs), X−ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and dynamic light scattering method (DLS) have been used. The results indicate that the ZnO−NAC−Cur NPs exhibit near−spherical morphology and uniform dispersion with an average diameter of ~70 nm. The hemolysis assay shows that ZnO−NAC−Cur NPs has almost no hemolytic activity. In addition, MTT cytotoxicity assessment on B16F10 murine melanoma cells present a drop of IC₅₀ values from 17.23 μg·mL⁻¹ (free curcumin) to 8.78 μg·mL⁻¹ (ZnO−NAC−Cur NPs). This result shows an augmented cancer−inhibitory effect of nanoconjugate complex. In conclusion, the novel ZnO−NAC−Cur NPs could be explored for new therapeutic endeavors.