Present study deals with the optimization of on-line solid phase extraction of Cu2+ using calix[4]arene based silica resin by the assessment of central composite design of response surface methodology. The immobilized resin was characterized with FT-IR and SEM techniques. The data obtained from experimental program of central composite design was used to model the parameters that significantly affect on Cu2+ extraction. The variables chosen were metal ion concentration, pH, and temperature. Second-order quadratic model was used to approximate the effect of variables on extraction efficiency. Furthermore, suggested model was also validated with the analysis of variance. The predicted values were in good agreement with experimental results, suggesting proficient application of central composite design as an economical alternative to acquire maximum amount of information for the modeling of on-line solid phase extraction with little number of experiments. Additionally, data obtained for different concentrations was analyzed by Freundlich, Langmuir, D-R isotherms, and Scatchard plot analysis. The results suggested that Langmuir isotherm was best fit model with R20.99, the energy calculated from D-R isotherm was 15.14KJ/mol suggesting that chemical force is involved in sorption process. The method was also validated for its linearity, accuracy, and precision.