In this work, the effect of gamma irradiation emitted by Cobalt 60 source has been investigated for the degradation of hydroxychloroquine (HCQ). The monitoring of the gamma irradiation treatment of HCQ aqueous solutions was followed by UV–visible, chemical oxygen demand, total organic carbon (TOC) and LC/MS analyses. Effects of several important parameters such as concentration, dose rate and pH on the degradation efficiency were studied then evaluated. Achieved results showed that % TOC removal efficiency of 98.5 was obtained after 8 kGy absorbed dose which warrants HCQ mineralization. The process was found to be more efficient when the initial pollutant concentration was low, with higher dose rate and at neutral pH. Furthermore, HCQ degradation kinetic study revealed a pseudo-first-order kinetic. Additionally, based on by-products identified by LC/MS, a degradation mechanistic schema mediated through hydroxyl radicals generated by water radiolysis has been proposed. Finally, in order to check the potential industrial application viability the energy consuming was evaluated.