It was aimed to develop and validate the UV spectroscopic, the first-order derivative spectroscopy, and the HPLC method for determination of cefuroxime axetil in bulk and tablets and also in spiked human plasma samples by UV spectroscopy method. In the spectroscopic analyses, the maximum absorbance of cefuroxime axetil in acetonitrile was obtained at 277 nm wavelength in the spectra. In first-order derivative spectroscopy method, two peaks were observed in spectra, a maximum at 258 nm and a minimum at 298 nm. 298 nm wavelength was used in the study. In HPLC-UV study, parameters were chosen as follows: C18 column, 0.1% acetic acid-acetonitrile (30:70; v/v) for mobile phase, 1.0 mL/min of flow rate, 280 nm of wavelength, 10 μL of injection volume and etodolac (2.5 μg/mL) as internal standard. Accuracy, precision, recovery, linearity and sensitivity parameters were determined for each of the three methods. Developed and validated methods were successfully applied on 4 tablets which are named as Cefaks, Cefurol, Aksef ve Enfexia. As a result, it is claimed that proposed method is sensitive, precise, accurate, and successfully used in quality control studies in the drug industry.