The presence of pharmaceutical compounds in water and soil has become an environmental concern. The aim of this study was to evaluate the performance of TiO₂ nanofiber in the oxidation of the antibiotic tetracycline. TiO₂ nanofiber was fabricated by electro-spinning method, and then was calcined at 560°C for 2 h. Central composite design (CCD) statistic model was used to optimize tetracycline concentration, time and pH for TiO₂ catalyst. A tubular Pyrex glass reactor with diameter of 15 cm and height of 30 cm was designed and a 125W Philips HPLN lamp (UV, λ > 254 nm) was used as light source. Samples were measured by high-performance liquid chromatography (HPLC). Equation of model suggests a direct relationship between pH and time with efficiency of tetracycline removal. The observations indicated that time is the most significant (scaled estimate = + 28.04) parameter in efficiency of tetracycline removal. The application of response surface methodology yielded the equation of Y = 65.82 + 5.74 pH + 28.04 time + (−3.07)(pH)² + (−6.6)(time)², with R² = 0.986 which represents good reliability of model. Based on the response surface plots optimum conditions for degradation of tetracycline with maximum efficiency of around 95% was attained. These conditions are as follow; concentration: 50 mg/l, pH= 8.3, time= 15 min.