An accurate, sensitive, precise and rapid gradient reversed-phase high-performance liquid chromatographic method was successfully developed and validated for the determination of doxycycline hyclate in bulk drug and tablets. The best separation was achieved on a 250 × 4.6 mm, 5.0 µm particle size CN Luna column with water + 0.1% TFA-acetonitrile + 0.1% TFA, 60:40 (v/v) as the mobile phase at a flow rate of 1.0 mL/min. Ultraviolet detection was performed at 360 nm at ambient column temperature (25°C). The method was linear over the concentration range of 50-100 µg/mL (r = 0.9999) with limits of detection and quantification of 2.83 and 8.59 µg/mL, respectively. The drug was subjected to oxidation, acid, base and neutral degradation, photolysis and heat as stress conditions. Degradation products were found interfering with the assay of doxycycline hyclate, therefore the method can be regarded as suitable. The method was applied for the determination of doxycycline hyclate in standard and pharmaceutical products, with excellent recoveries. The method can be used for the quality control of doxycycline hyclate.