A numerical method is developed for the initial guesses of heat transfer and kinetic parameters in a wall-cooled fixed-bed reactor accompanied with side-stream analysis in both the axial and radial directions. The differential method is found to be the only way to decouple the heat and mass transport equations, and thus enables the estimation of the heat transfer and kinetic parameters by separate steps. Compared with simultaneous estimation by the integral methods, the differential method possesses a unique advantage arising from the separate estimation of the parameters, because the pararnetric correlation can be reduced since the parameter number in the separate estimating process is less than that in the integral process. Numerical analysis and experimental studies reveal that the most appropriate method for presenting the axial derivative is by the Pade approximation, and that for the radial derivatives is by the orthogonal collocation with one point.