With the increasing abuse of antibiotics, more attention has been focused on the potential harm on ecological environment and human health. The aim of this study was quantitative analysis of ceftazidime using Surface Enhanced Raman spectroscopy (SERS). Flower-shaped silver nanoparticles adsorbed on silicon wafer were fabricated in an aqueous medium without heavy metal or organic wastes. The limits of detection (LOD) of Rhodamine 6G (R6G) could reached to 10<sup>-9</sup> M, indicating that the substrates had high SERS activity. Meanwhile, the substrates showed excellent stability and uniformity. Flower-shaped silver nanoparticles substrates were selected as substrates for detecting the SERS spectra of ceftazidime in different concentrations. The information about the structure of ceftazidime molecule was reflect by Raman vibration assignments efficiently. Based on the Raman characteristic bands of ceftazidime, four quantitative analysis models using linear regression were compared. It was found that equation between log<sub>10</sub>C (C refers to the concentration of ceftazidime) and Iavg (average intensity) of Raman characteristic bands (749 cm<sup>-1</sup> , 850 cm<sup>-1</sup> and 1025 cm<sup>-1</sup>) was more suitable for quantitative analysis of ceftazidime, and correlation coefficient R<sup>2</sup> was up to 0.96. The quantitative model was used to detect the concentration of ceftazidime in practical surface water sample (10<sup>-2</sup> g/L), and the relative error between actual values and calculated values was 1.95%. This method is high sensitivity and rapid, which is potentially a powerful tool for quantitative analysis of other antibiotics.