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Isomerization process is considered one of the main processes used to produce high octane rating gasoline with improved environmental conditions and less emissions. The main keys of performance in isomerization units are the product yield, paraffin isomerization number (PIN) and octane number (RON). In this article we present a multi-response optimization strategy for an industrial naphtha continuous isomerization-process that aims to maximize RON, PIN and yield. Data of 53-runs including feed compositions as well as operating conditions; reactor temperature, benzene content, liquid hour space velocity, feed PIN, hydrogen to hydrocarbon ratio, feed octane number, C7+ content, inlet reactor temperature and iC5/C5P ratio are collected from a refinery company over a period of two months to test the effect of each variable and their interaction over each response individually using analysis of variance (ANOVA). Model reduction is applied for the three models in order to exclude any insignificant data and improve the model's accuracy. Finally, the optimum operating conditions for the process are selected using numerical optimization in Design Expert 11 by comparing with the real industrial data runs to give the maximum yield, PIN and RON which are 99.992, 122 and 86 respectively. Benzene content is selected to be 1.807 wt%, reactor temperature;143 o C, LHSV; 0.882 h-1 , feed PIN; 64.611, H 2 /HC; 0.07, feed RON; 74.408, C7+; 4.06 wt%, inlet reactor temperature; 116 o C and iC5/C5P ratio 45.768.