A supercritical fluid, such as supercritical carbon dioxide (scCO2) is increasingly used for the micronization of pharmaceuticals in the recent past.The role of scCO2as a green solvent in supercritical fluid (SCF) process is decided by the solubility information of the pharmaceutical compound in scCO2. The commonly used SCF processes are the rapid expansion of supercritical solution (RESS) and supercritical antisolvent precipitation (SAS). To implement micronization process, solubility of pharmaceuticals in scCO2is required. Present study is aimed at both measuring and modeling of solubilities of hydroxychloroquine sulfate (HCQS) in scCO2. Experiments were conducted at various conditions (P = 12 to 27 MPa and T = 308 to 338 K), for the first time. The measured solubilities were found to be ranging between (0.0304 × 10–4and 0.1459 × 10–4) at 308 K, (0.0627 × 10–4and 0.3158 × 10–4) at 318 K, (0.0982 × 10–4and 0.4351 × 10–4) at 328 K, (0.1398 × 10–4and 0.5515 × 10–4) at 338 K. To expand the usage of the data, various models were tested. For the modelling task existing models (Chrastil, reformulated Chrastil, Méndez-Santiago and Teja (MST), Bartle et al., Reddy-Garlapati, Sodeifian et al., models) and new set of solvate complex models were considered. Among the all models investigated Reddy-Garlapati and new solvate complex models are able to fit the data with the least error. Finally, the total and solvation enthalpies of HCQS in scCO2were calculated with the help of model constants obtained from Chrastil, reformulated Chrastil and Bartle et al., models.