A novel method for the quantitative determination of ranitidine hydrochloride (RNH) based on the fluorescence quenching of functionalised CdS quantum dots (QDs) by RNH in aqueous solution was proposed. The method is simple, rapid, specific and highly sensitive with good precision. The thioglycolic acid (TGA)-capped CdS QDs were synthesized from cadmium nitrate and sodium sulfide in alkaline solution. Under the optimal conditions, the Stern-Volmer calibration plot of F(0)/F against concentration of RNH was linear in the range of 0.50-15.0 μg mL(-1) with a correlation coefficient of 0.996. The limit of detection (LOD) was 0.38 μg mL(-1). The method was satisfactorily applied to the direct determination of RNH in pharmaceutical formulations with no significant interference from excipients. The results were found to be in good agreement with those obtained by the reference method and the claimed value. The accuracy and reliability of the method were further ascertained by recovery studies via the standard-addition method, with percentage recoveries in the range of 98.47 to 102.30%. The possible fluorescence quenching mechanism for the reaction was also discussed.