In this study, the interaction of hydrochlorothiazide (HCT), benzothiadiazine diuretic, with cationic surfactant cetyltrimethylammonium bromide (CTAB) was investigated. The effect of cationic micelles on the spectroscopic and acid–base properties of HCT was studied at pH 10.5. The binding of HCT to CTAB micelles implied a shift in drug acidity constant (pKawater−pKamicelle=0.46) proving the greater affinity of HCT dianion for the positively charged CTAB micelle surface. From the dependence of differential absorbance at λ=355nm on CTAB concentration, by using mathematical model that treats the solubilization of HCT dianion as its binding to specific sites in the micelles (Langmuir adsorption isotherm), the binding constant K b =(1.17±0.16)×10 4 mol −1 dm 3 was obtained. By using pseudo-phase model, the partition coefficient between the bulk water and CTAB micelles, K x , was calculated from both differential absorbance ΔA 355 , K x =(6.18±0.64)×10 4 mol (1 dm 3 , and first-order derivative amplitude 1 D 250.1 , K x =(5.47±0.56)×10 4 mol (1 dm 3 .