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Photodynamic therapy (PDT) uses a combination of photosensitizers with visible light to generate reactive species and selectively kill tumor or unwanted tissue. Znln 2 S 4 nanoparticles are widely implemented in photovoltaic device materials and photolysis water catalysts owing to their unique photoelectric properties. Whether Znln 2 S 4 itself can be used as an effective dye in PDT is still unknown. To determine the effects and potential mechanism of Znln 2 S 4 PDT on HepG2 cell apoptosis, electron microscopic analysis was performed to monitor the apoptotic morphology of HepG2 cells upon exposure to Znln 2 S 4 -PDT. Flow cytometry was performed to measure the apoptosis rate and intracellular ROS production. Western blot and ELISA were performed to reveal the expression changes in Bax, caspase-3 and caspase-9. Data from this work suggested that cells exhibited the typical apoptotic morphology in response to Znln 2 S 4 -PDT, with high apoptotic rate. The intracellular ROS production after Znln 2 S 4 -PDT occurred in a dose-dependent manner. Moreover, Znln 2 S 4 -PDT augmented the expression levels of pro-apoptosis factors, especially, Bax, caspase-3 and caspase-9. Taken together, our novel findings, Znln 2 S 4 -PDT elicited HepG2 cell apoptosis, suggesting Znln 2 S 4 as a promising photosensitizer candidate for cancer therapy.