Diazinon (DZN), a broad-spectrum and highly effective organophosphorus pesticide, is widely being used in agricultural production and household environments. However, massive DZN effluent can be generated during the DZN production process, which will cause devastating effects on the ecosystem and damage human health due to the improper dispose of pesticide effluent before discharging. In this work, hydrodynamic cavitation (HC), a new advanced oxidation technology, was used to degrade DZN in wastewater for the first time. The influences of DZN initial concentration (5.0–15 mg/L), solution pH (4.0–10), temperature (30–50 °C) and some orifice plate geometric parameters (orifice numbers and orifice half angles) on the degradation effect of DZN were investigated. It can be observed that the DZN in solution can be effectively degraded in orifice plate HC system based on three orifices with 45° convergent half angle and the degradation ratio can reach 50.52 % under the operation conditions of 150 min treatment time, 30 °C temperature and pH = 4.0 acidity. Subsequently, the studies of intensifying DZN degradation were also carried out through adding different inorganic oxidants such as potassium peroxodisulfate (K2S2O8), potassium periodate (KIO4) and sodium perchlorate (NaClO4). The maximum DZN HC degradation extent (81.92 %) can be achieved in the presence of K2S2O8 under the optimized conditions. The generated intermediate products in DZN HC degradation process are some low-toxic and low-active substances. And that, these intermediate products can be further mineralized to H2O, CO2 and inorganic ions. On the basis of cavitational yield, the energy consumption analysis has been performed. Overall, this work demonstrates that the HC combined with oxidant K2S2O8 may be a promising strategy for the large-scale treatment of organophosphorus pesticide wastewater.