Four simple, sensitive, accurate and precise stability-indicating methods were developed for determination of sofosbuvir (SFB) in pure form as well as in its pharmaceutical preparation and in presence of its alkaline degradate. The first method is an HPLC stability–indicating method, where the intact drug (SFB), the internal standard (atorvastatin) and SFB degradation product were separated on a Athena C₁₈ (250 mm X 4.6 mm ID, 5µm particle size) column using methanol–water (70:30, v/v) as a mobile phase at a flow rate of 1 ml/min and UV detection at 260 nm. The second method is the ratio difference method, where the UV absorption spectra of different concentrations of SFB were divided by the absorption spectrum of a certain concentration (30 µg /ml) of its degradation product (divisor) to get the ratio difference spectra. Afterwards, the difference in peak amplitudes between 270 and 245 nm were measured. The third method is the ratio derivative method, where the amplitudes of first derivative of the obtained ratio difference spectra were measured at 282 nm. The fourth method is the mean centering of ratio difference spectra, where the amplitudes of the mean centered ratio difference spectra were measured at 262.6 nm. The calibration curves were linear over the concentration range of 5-35 µg/ml for all methods. The proposed methods can selectively analyse the drug in presence of up to 86 % of its degradation product with mean recoveries of 100.66±1.310, 101.04±1.662, 101.06±1.026 and 99.92+1.374 for the four methods, respectively. These methods were validated and successfully applied for the determination of SFB in its commercial preparation. Moreover, the obtained results were statistically compared with those of the reported method by applying t-test and F-test at 95% confidence level. It was found that no significant differences were observed regarding accuracy and precision.