Diesel pilot high-pressure direct injection (HPDI) natural gas technology has been noticed and applied in medium and heavy-duty engines due to its outstanding economy and power performance. However, the combustion of two kinds of fuels will involve more injection parameters, which increases the difficulty of designing injection strategy and calibrating injection parameters. This paper investigates comprehensively the effects of three key engine injection parameters (injection timing, injection duration of the pilot diesel, interval of injection between diesel and natural gas) on the engine ignition delay and cylinder pressure evolution using the experimentation method, which are utilized to guide the design of injection strategy and optimize injection parameters. Results show that the maximum in-cylinder pressure and its position are determined by the injection timing of natural gas, but little affected by the injection parameters of diesel. As the injection timing advances and the duration of diesel injection shortens, the ignition delay increases. To avoid rough combustion in the cylinder, it is necessary to optimize the injection timing, injection interval, and ignition diesel injection duration to ensure that the pressure rise rate does not exceed the threshold.