The solubility of the antifungal drug fluconazole in buffer solutions of different acidity (pH 1.2, 2.0 and 7.4), 1-octanol and hexane in the temperature range (293.15–313.15) K is determined by the isothermal saturation method. The solubility of the compound in selected solvents increases as follows: hexane, buffer pH 7.4, buffer pH 2.0, 1- octanol, buffer pH 1.2, and does not exceed 0.2 mol·l−1. The temperature dependence of fluconazole saturated vapor pressure is obtained by the transpiration method. The sublimation enthalpy of the compound equals 131.4 ± 0.9 kJ·mol−1. Based on the HYBOT descriptors, it is shown that it is possible to estimate the sublimation enthalpy of compounds structurally similar to fluconazole.