Diclofenac sodium, a widely detected pharmaceutical drug in wastewater samples, has been selected as a model pollutant for degradation using novel combined approach of hydrodynamic cavitation and heterogeneous photocatalysis. A slit venturi has been used as cavitating device in the hydrodynamic cavitation reactor. The effect of various operating parameters such as inlet fluid pressure (2–4bar) and initial pH of the solution (4–7.5) on the extent of degradation have been studied. The maximum extent of degradation of diclofenac sodium was obtained at inlet fluid pressure of 3bar and initial pH as 4 using hydrodynamic cavitation alone. The loadings of TiO 2 and H 2 O 2 have been optimised to maximise the extent of degradation of diclofenac sodium. Kinetic study revealed that the degradation of diclofenac sodium fitted first order kinetics over the selected range of operating protocols. It has been observed that combination of hydrodynamic cavitation with UV, UV/TiO 2 and UV/TiO 2 /H 2 O 2 results in enhanced extents of degradation as compared to the individual schemes. The maximum extent of degradation as 95% with 76% reduction in TOC has been observed using hydrodynamic cavitation in conjunction with UV/TiO 2 /H 2 O 2 under the optimised operating conditions. The diclofenac sodium degradation byproducts have been identified using LC/MS analysis.