A sensitive, selective and efficient sensor based on carbon paste electrode modified by newly synthesized mesoporous silica nanoparticles (MSNs/CPE) is proposed for electrochemical determination of tyrosine(Tyr) and tryptophan (Trp). In the proposed synthesis procedure of MSN, a weak acid such as NH4NO3has been used in the washing stage, instead of strong acid, HCl. Brunauer–Emmett–Teller, BET, and Barrett–Joyner–Halenda (BJH) analyses confirms that the creation of cavities in MSN was happen more efficiently when NH4NO3was applied respect to HCl procedure. Moreover, the obtained result shows the superiority of proposed approach compared with the unmodified carbon paste electrode, CPE; reported result for commercial SiO2 modified electrode, SiO2/CPE, and also MSN/CPE by HCl procedure, such that the oxidation peak current improved significantly for both amino acids. After optimization of experimen-tal parameters, the oxidation peak current of Trp was linear over a concentration range of 0.05–600 M with a detection limit of 1.13 × 10?8M. Similarly, the concentration range for Tyr, based on oxidation peak current, was in the range from 0.3–600 M with limit of detection 4.97 × 10?8M. Finally, since the differential pulse voltammetric peaks of Trp and Tyr has severe overlapping degree, the clustering ofvariables concept based PLS has been used as an efficient variable selection algorithm for simultaneousdetermination of Tyr and Trp. The results demonstrated that the variable clustering combined with PLS can split the voltammogram spectra into useful and redundant ones and then based on informative cluster, stable model can be reached. Analysis of artificial urine as a real sample, confirms the potential ability of the proposed method for simultaneous determination of these amino acids.