The parameters of lipophilicity of spironolactone (a single member of steroids group), which is widely applied as diuretic and antihypertensive agent, were experimentally determined by reversed-phase TLC and HPLC methods as well as calculated using different computer programs and also by a novel mode based on topological indices. Various stationary phases, such as RP-18WFA4254, RP-2F254, RP-18F254 and also different binary solvent systems composed of organic modifier (e.g., methanol, dioxane, acetone) and water were used as mobile phases in order to predict the following chromatographic parameters: Rm, and logkw, respectively. LogP of examined spironolactone calculated with respective theoretical procedures: AlogPs, logPKOWWIN, xlogP2, xlogP3, AClogP, AlogP, MlogP and also logPaverage were obtained from online package software. The partition coefficients expressed as logP1, logP2 and logP3 were calculated by means of the formulae based on the numerical values of the following topological indices: , 0B, 1B, W, 0χv and IB, which was novelty of this study. A good agreement between logP calculated by new method and experimentally estimated lipophilicity parameters (by chromatography and by shake flask method) was found. The results confirmed applicability of the topological indices for calculating lipophilicity of spironolactone as alternative procedure to the experimental and other computed logP values.