High performance liquid chromatography of drugs is usually performed with the help of organic mobile phase like Methanol, Acetonitrile etc., which are toxic and expensive.In the present study, hydrotropic solution was employed as mobile phase for the estimation of poorly aqueous soluble drug Cefixime by HPLC.The analysis was carried out on Agilent 1220 Infinity LC (G4288C) model which consists of Agilent 1220 infinity LC pump, Rheodyne injector (20μL loop) and Variable wavelength detector. The analytical column used was Agilent eclipse plus C18 (4.6 x 100mm) with 3.5 μm particle size.An aqueous 6% sodium acetate (pH adjusted to 6.2 by acetic acid) at a flow rate of 1.0mL/minute was employed as mobile phase and the drug was detected at 290 nm at ambient temperature. The method was validated as per ICH guidelines. The retention time for Cefixime was found to be 2.34 min. Linearity was observed in the concentration range of 40-240 μg/mL with correlation coefficient 0.9999.The percentage of relative standard deviation of six replicate measurements was found to be 0.0055. This indicates the proposed method was precise. Recovery studies were conducted at three different concentration levels within the linearity limits and the average percentage in tablet dosage form was determined and found to be 99.54%. Therefore, the developed method employing hydrotropic solution as mobile phase was novel, simple, precise, cost-effective, eco-friendly, safe and can be successfully applied for the estimation of Cefixime in pharmaceutical dosage forms.