This inquiry aimed to examine the mechanism of separation of candesartan and hydrochlorothiazide, two frequently prescribed antihypertensive medications, using hydrophilic interaction liquid chromatography (HILIC) in conjunction with ultraviolet detection. The research utilized two laboratory-manufactured hydrophilic interaction liquid chromatography (HILIC) columns, specifically ZIC2 and ZIC5, which exhibited variations in the inter-ionic site group distances. To establish the methodologies, the present study investigated the impact of diverse HILIC mode parameters, including acetonitrile content, pH, and acetate buffer concentration in the mobile phase. The chromatographic separation was executed utilizing a ZIC-HILIC column with a length of 100 mm, an inner diameter of 4.6 mm, and a particle size of 3.5 µm. The mobile phase comprised an acetate buffer with a concentration of 30 mM and a pH of 4.75, along with acetonitrile in a ratio of 20:80 (v/v). The detection of ultraviolet light was performed at a wavelength of 254 nanometers. The study established the linearity ranges of candesartan and hydrochlorothiazide to be 0.06-17 µg/ml and 0.02-11.5 µg/ml, respectively. The pharmaceutical preparations were analyzed for the percentage recoveries of candesartan and hydrochlorothiazide. The mean percentage recoveries of candesartan ranged from 98.12% to 100.37%, while the mean percentage recoveries of hydrochlorothiazide ranged from 99.48% to 100.48%. The efficacy of this technique in precisely ascertaining the constituents of hydrochlorothiazide and candesartan in pharmaceutical formulations has been demonstrated.