The solubility of 5-fluorouracil (5 -FU), a widely used chemotherapeutic agent to treat solid tumors, which include colorectal, head and neck, breast, and lung cancer, was determined at temperatures ranging from 278.15 to 333.15 K in 11 pure solvents and binary water + ethanol solvent mixtures using the polythermal method. It was demonstrated that the solubility of 5 -FU increases with increasing temperature in the pure solvents and at constant solvent composition in the solvent mixtures. Moreover, the solubility of 5 -FU in the solvent mixtures exceeds its solubility in pure water and ethanol. The experimental solubility data of 5 -FU in the pure solvents and solvent mixtures were correlated using the modified Apelblat and gamma h model equations. The predicted solubility data obtained agree with the experimental data based on the calculated relative deviation (RD) and the average relative deviation (ARD%) values. The selected solvents are categorized as either Class 2 or 3 (less toxic and lower risk to human health) solvents, and hence the correlated and experimentally derived solubility data of 5 -FU presented provide a pathway to develop and engineer enhanced pharmaceutical processes and products based on this compound.