Abstract Collapse of cavitation bubbles generates extremely high local pressures and temperatures that can be utilized for generating hydroxyl radicals as strong oxidizing agents. The existence of hydroxyl is known as a main reason for the chemical degradation of solute molecules. In this paper, the operating pressure, inlet pressure, flow rate, and consequently cavitation number in a venturi type hydrodynamic cavitation reactor were controlled and systematically varied. In the case of non-VOC solutions, it is difficult to obtain great extension degradation with just cavitation or that the removal is limited to small percentage. Instead, the contribution of cavitation flow and H 2 O 2 injection, called enhanced cavitation–oxidation process (ECOP) was introduced for the degradation of non-VOC solutions. In this regard, effects of the cavitation number, injection duration, and quantity of H 2 O 2 injection on degradation rate of 2-Chlorophenol were investigated. It was experimentally demonstrated that the degradation rate of 2-Chlorophenol increased with an increase in the injected amount of H 2 O 2 . A similar effect was also observed when injection duration was reduced for a fixed quantity of H 2 O 2 . In addition, effects of H 2 O 2 injection on cavitation regime and extent of cavitation zone were studied. Moreover, it was found that the injected amount of H 2 O 2 had a major effect on the degradation of 2-Chlorophenol compared to the minor effect of cavitation number over the entire range of cavitation number. Comprehensive yield efficiency analysis was also performed, which showed that, for an energy efficient operation, ECOP was required to operate with mild cavitating flow, high injected magnitude of H 2 O 2 , and short injection duration; however, for fast decomposing ECOP, intense cavitating flow was required.