Unfortunately, malaria still remains a major problem in tropical areas, and it takes thousands of lives each year and causes millions of infected cases. Besides, on December 2019, a new virus known as coronavirus appeared, that its rapid prevalence caused the World Health Organization (WHO) to consider it a pandemic. As a potential drug for controlling or treating these two undesired diseases at the cellular level, chloroquine and its derivatives are being investigated, although they possess side effects, which must be reduced for effective and safe treatments. With respect to the importance of this medicine, the current research aimed to calculate the solubility of chloroquine in supercritical carbon dioxide, and evaluated effect of pressure and temperature on the solubility. The pressure varied between 120 and 400 bar, and temperatures between 308 and 338 K were set for the measurements. The experimental results revealed that the solubility of chloroquine lies between 1.64 × 10−5 to 8.92 × 10−4 (mole fraction) with different functionality to temperature and pressure. Although the solubility was indicated to be strong function of pressure and temperature, the effect of temperature was more profound and complicated. A crossover pressure point was found in the solubility measurements, which indicated similar behaviour to an inflection point. For the pressures higher than the crossover point, the temperature indicated direct effect on the solubility of chloroquine. On the other hand, for pressures less than the crossover point, temperature enhancement led to a reduction in the solubility of chloroquine. Moreover, the obtained solubility results were correlated via semi-empirical density-based thermodynamic correlations. Five correlations were studied including: Kumar & Johnston, Mendez-Santiago-Teja, Chrastil, Bartle et al., and Garlapati & Madras. The best performance was obtained for Mendez-Santiago-Teja's correlation in terms of average absolute relative deviation percent (12.0%), while the other examined models showed almost the same performance for prediction of chloroquine solubility. © 2020 Elsevier B.V.