In order to better understand the heat transfer process with the pyrolysis of hydrocarbon fuel, the pyrolysis effect on heat transfer characteristics in the mini-channel was comprehensively investigated in this work. First, the heat transfer characteristics were experimentally measured, and the thermophysical properties of fuel were calculated according to the species distribution. Then, the heat transfer and thermophysical properties in an ideal condition (no pyrolysis in the same heat flux) were simulated by a numerical method. By comparing the experimental results with the simulation results, it could be found that pyrolysis can significantly inhibit the rising of fuel temperature up to 332 K. Meanwhile, pyrolysis can significantly decrease the density, increase the viscosity and thermal conductivity, and keep the specific heat capacity approximately at a constant. Then, the variation of thermal properties can decrease the Reynold number and Prandtl number, thus impairing the heat transfer performance. However, while pyrolysis occurs from a mild degree to a deep degree, the heat transfer will be enhanced. This phenomenon may be caused by the dramatic difference of pyrolysis in the radial direction. At the same time, in the high-temperature region, the percentages of the chemical heat sink in the total heat sink are all over 50%. Especially in these low mass flux conditions, the percentages of chemical heat sink can be up to 65%. According to the results of this work, both the negative and positive effect of pyrolysis should be taken into consideration in cooling structure design.