This study investigates the photocatalysis of dissolved organic matter (DOM) under ZnO-assisted artificial sunlight irradiation. Response surface methodology (RSM) based on central composite design (CCD) was utilized for design of experiments with ZnO dosage and pH. Fluorescence excitation-emission matrices coupled with parallel factor analysis (EEM-PARAFAC), dissolved organic carbon (DOC), and UV/Vis spectroscopy were used to track the DOM degradation during photocatalysis. EEM-PARAFAC analysis decomposed fluorescent DOM into two components (C1 and C2), identified as terrestrial humic-like organic matters. A pseudo-first-order DOM removal decreased with increased ZnO dosage, and were highest at pH 7 and lowest at pH 4. Response surface models of DOC, UV254, C1 and C2 removals demonstrated statistically significant and well matched with a second-order polynomial equation based on analysis of variance (ANOVA). First-order terms were the highest contributor, in which ZnO dosage had the highest level of significance, to the DOM removal. The optimal conditions for the photocatalysis of DOM were found to be ZnO 0.3 g/L and pH 10, showing that the removals of DOC, UV254, C1 and C2 were 57.9%, 94.5%, 100%, and 98.0%, respectively. In addition, ZnO showed a good stability and better photodegradation efficiency than TiO2 in the DOM removal.