The application of a hybrid framework based on the combination, artificial neural network-genetic algorithm (ANN-GA), for n-thymol synthesis modeling and optimization has been developed. The effects of molar ratio propylene/cresol (X1), catalyst mass (X2) and temperature (X3) on n-thymol selectivity Y1 and m-cresol conversion Y2 were studied. A 3-8-2 ANN model was found to be very suitable for reaction modeling. The multiobjective optimization, led to optimal operating conditions (0.55 ? X1 ? 0.77; 1.773 g ? X2 ? 1.86 g; 289.74 °C ? X3 ? 291.33 °C) representing good solutions for obtaining high n-thymol selectivity and high m-cresol conversion. This optimal zone corresponded to n-thymol selectivity and m-cresol conversion ranging respectively in the interval [79.3; 79.5]% and [13.4 %; 23.7]%. These results were better than those obtained with a sequential method based on experimental design for which, optimum conditions led to n-thymol selectivity and m-cresol conversion values respectively equal to 67% and 11%. The hybrid method ANN-GA showed its ability to solve complex problems with a good fitting.