ObjectivesZinc sulfide nanoparticles (ZnS NPs), as one of the quantum dots less than 10 nm, possess unique size‐dependent autofluorescence. Excitation of their valence electrons by energy higher than the bandgap reveals the ZnS NPs' inherited photocatalysis with additive cytotoxic consequences of reactive oxygen species (ROS) release. Coupling the cytotoxicity of photoactivated ZnS NPs with their autofluorescence would be a novel theranostic modality, combating superficially accessible carcinoma.Material and methodsAfter synthesizing and characterization of ZnS NPs, we verified their photocatalysis and electron donation upon UV excitation in degrading organic dye and DNA cleavage, respectively. We then tested the efficacy of UV‐activated ZnS NPs to induce ROS‐dependent apoptosis in squamous cell carcinoma and breast cancer cell lines.ResultsThe energetic electron–hole pairs generated upon UV excitation of ZnS NPs with the consequent cascade of ROS release revealed potent apoptotic cancer cell deaths, compared with single treatment modalities of nonexcited nanoparticles and UV. Moreover, the inherited luminescence of ZnS NPs enabled visualization of their predominant intracytoplasmic uptake with tracking of their cellular response.ConclusionThe intensified luminescence and the fortified cytotoxicity of photoactivated ZnS NPs enhance their theranostic qualifications, boosting their antitumorigenic use.