Based on three-dimensional (3D) computational fluid dynamics (CFD) software, a 3D numerical model was constructed to investigate the effects of injection timing, pilot diesel energetic ratio (PDER), and angle between the central axis of the diesel jet and the horizontal direction (α) on combustion and knock in the natural gas mixing-limited combustion (NMLC) mode and natural gas slightly premixed combustion (NSPC) mode. The results indicate that advancing the start of injection of natural gas (NSOI) leads to a slight improvement in indicated thermal efficiency (ITE), but also an increase in peak cylinder pressure (Pmax) and maximum pressure rise rate (MPRR). In the NMLC mode, as the diesel and natural gas injection interval (IDN) decreases, the interference between the diesel and natural gas jets intensifies, ultimately leading to instability in the flame propagation process and increased fluctuations in cylinder pressure. At different NSOIs, when IDN is 0°CA, the maximum amplitude of pressure oscillations (MAPO) is the highest. When the PDER is increased from 5 % to 15 %, ITE increases by 7.1 %. Under different combustion modes, as α increases, ITE first increases and then decreases. However, the NSPC mode achieves a higher ITE, reaching up to 44.4 %.