Determination of the optimal model parameters for biochemical systems is a time consuming iterative process. In this study, a novel hybrid differential evolution (DE) algorithm based on the differential evolution technique and a local search strategy is developed for solving kinetic parameter estimation problems. By combining the merits of DE with Gauss-Newton method, the proposed hybrid approach employs a DE algorithm for identifying promising regions of the solution space followed by use of Gauss-Newton method to determine the optimum in the identified regions. Some well-known benchmark estimation problems are utilized to test the efficiency and the robustness of the proposed algorithm compared to other methods in literature. The comparison indicates that the present hybrid algorithm outperforms other estimation techniques in terms of the global searching ability and the convergence speed. Additionally, the estimation of kinetic model parameters for a feed batch fermentor is carried out to test the applicability of the proposed algorithm. The result suggests that the method can be used to estimate suitable values of model parameters for a complex mathematical model. Determination of the optimal model parameters for biochemical systems is a time consuming iterative process. In this study, a novel hybrid differential evolution (DE) algorithm based on the differential evolution technique and a local search strategy is developed for solving kinetic parameter estimation problems. By combining the merits of DE with Gauss-Newton method, the proposed hybridization approach employing a DE algorithm for identifying promising regions of the solution space followed by use of Gauss-Newton method to determine the optimum in the identified regions. problems are utilized to test the efficiency and the robustness of the proposed algorithm compared to other methods in literature. The comparison says that the present hybrid algorithm outperforms other estimation techniques in terms of terms of the global searching ability and the convergence speed. kinetic model parameters for a feed batch fermentor is carried out to test the applicability of the proposed algorithm. The result suggests that the method can be used to estimate suitable values ​​of model parameters for a complex mathematical model.