Photodynamic therapy (PDT) uses a combination of photosensitizers with visible light to generate reactive species and selectively kill tumor or unwanted tissue. Znln2S4 nanoparticles are widely implemented in photovoltaic device materials and photolysis water catalysts owing to their unique photoelectric properties. Whether Znln2S4 itself can be used as an effective dye in PDT is still unknown. To determine the effects and potential mechanism of Znln2S4PDT on HepG2 cell apoptosis, electron microscopic analysis was performed to monitor the apoptotic morphology of HepG2 cells upon exposure to Znln2S4-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 Znln2S4-PDT, with high apoptotic rate. The intracellular ROS production after Znln2S4-PDT occurred in a dose-dependent manner. Moreover, Znln2S4-PDT augmented the expression levels of pro-apoptosis factors, especially, Bax, caspase-3 and caspase-9. Taken together, our novel findings, Znln2S4-PDT elicited HepG2 cell apoptosis, suggesting Znln2S4 as a promising photosensitizer candidate for cancer therapy.