A quantitative method using diffuse reflectance infrared fourier transform spectroscopy (DRIFTS) was developed and validated for the estimation of hydrochlorothiazide (HCTZ) in its tablet dosage form. The solid-state samples were, prepared by dilution in dry potassium bromide and were analyzed by FTIR spectrophotometer with DRIFT sampling technique. A linear relationship for the sulphone peak area centered on 1151 cm−1 was observed in the range of 1-6 % w/w with good correlation coefficient of 0.999. The percent recovery of hydrochlorothiazide in marketed tablet dosage form was in the range of 100 ± 0.3071. The present reported method is precise, reproducible, and eco-friendly. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) may have a potential as an alternative method for qualitative and quantitative analysis of hydrochlorothiazide in bulk drugs and tablet dosage forms.