In this study compound-specific isotope analysis (CSIA) has been used to explore the degradation mechanism of nano titanium dioxide (TiO₂) catalyzes photodegradation of diethyl phthalate (DEP). TiO₂ is a popular photosensitizer with potential in waste water treatment and application in advanced oxidation processes. The degradation process of DEP can be described with a first-order kinetics in the applied concentration ranges. The larger degradation rate constant has been found at neutral conditions. The ¹³C and ²H isotope fractionation associated with the nano TiO₂ catalyzes photodegradation of DEP at pH 3, 7 and 11 yield normal isotope effects. In the TiO₂/UV/DEP and TiO₂/H₂O₂/UV/DEP systems, the correlation of ¹³C and ²H fractionation (Λ) were calculated to be 2.7 ± 0.2, 2.8 ± 0.2 at pH 3, 2.2 ± 0.4, 2.5 ± 0.2, 2.3 ± 0.6 at pH 7 and 2.6 ± 0.3, 2.2 ± 0.3, 2.7 ± 0.2 and 2.3 ± 0.3 at pH11, respectively. The dominant free radical species in studied systems were explored by combining free radical quenching method and electron paramagnetic resonance analysis. The hydroxyl radicals have been found as the main radical species at all pH conditions studied. Furthermore, the ¹³C and ²H fractionation suggested that the addition of •OH on the benzene ring of DEP is the main conversion pathway. Therefore, CSIA is a promising technology for the identification of reaction pathways of DEP for example in water treatment systems.