In this work, a detailed combined chemical kinetics mechanism (76 chemical species, 464 reactions) for a mixture of natural gas and n-heptane with arbitrary mass fractions of natural gas between 36 and 85 percent was developed from the combination of the detailed reaction schemes for natural gas and n-heptane fuels. Then, essential reactions were determined through performing a sensitivity analysis on the combined mechanism. In addition, genetic algorithm was applied to optimize the Arrhenius rate coefficients of the specified reactions by means of sensitivity analysis. Finally, accuracy of the presented mechanism was investigated through two different zone configurations (6 zones and 11 ones) of a multi-zone combustion model as well as available laboratory results. Also, the results of the two considered zone configurations from the multi-zone combustion model were compared, whereby it was found that the two zone configurations considered could properly predict combustion, performance parameters (i.e. start of combustion), burn duration, indicated mean effective pressure, indicated thermal efficiency as well as important HCCI engine emissions (i.e. unburned HC and CO emissions) in good accord with the experimental data. Also, it was discovered that the results of the 6 zone combustion model were closer to the results of the 11 zone combustion model. But the required computational time for the 11 zone combustion model was approximately twice that of the 6 zone combustion model.