This article carried out a numerical investigation of knock, using the Taguchi method and the grey relational analysis method to determine the importance and the contribution rate of multiple parameters on the peak pressure in the cylinder and the knock tendency under heavy load conditions. Four parameters, namely, compression ratio, spark timing, EGR rate, and inlet temperature, were set at four levels. The simulation was designed using a design of experiment method based on Taguchi's L16 orthogonal array. The simulation results of knock tendency and peak in-cylinder pressure were analyzed by the Taguchi-Grey method. According to the analysis results of the Taguchi-Grey method, the optimal level, the importance rank, and the contribution rate of factors on the knock tendency, peak in-cylinder pressure, and equivalent response were determined. The results demonstrate that the contribution rate of compression ratio, spark timing, EGR rate, and inlet temperature to the knock tendency is 45.9%, 22.98%, 19.46%, and 11.66%, respectively. The compression ratio, spark timing, EGR rate, and inlet temperature contribution to the peak in-cylinder pressure is 40.56%, 31.03%, 24.94 and 3.47%, respectively. The optimal conditions for the minimum knock tendency and the maximum peak in-cylinder pressure are obtained at CR1 EGR4 IT1 ST1 and CR4 EGR1 IT1 ST4, respectively.