An in situ acetylation solid phase microextraction（SPME）/gas chromatography-mass spectrometry was developed for the determination of phenolic compounds in water using central composite designs of the response surface methodology in the process of optimization experiments.Three important response factors,namely derivatization reagent（acetic anhydride）,derivatization agent（Na2HPO4） and reaction/extraction temperature,confirmed by the single factor experiments to be the continuous variables of non monotonic change in the derivatization and extraction processes were selected.Taking the normalized peak area,ie.the dependent variable representing relative extraction efficiency,as the optimizing target,quantitative relationships between the relative extraction amount and the three independent factors were established with the backward multi regression fitting.Results of the variance analysis revealed the regression was significant with the lowest F and P value at 63 and 0002 8,respectively.In addition,the variance analysis indicated that the temperature effect was the most significant,the amount of Na2HPO4 next and acetic anhydride the least. Results also showed that the optimum conditions were quite different for different phenolic compounds,since the reaction / extraction temperatures were related to their boiling points and the Na2HPO4 amount was related to their dissociation constants（pKa）.