In order to research the influence of different injection strategies on the performance of heavy-duty diesel engines under high altitude conditions, a three-dimensional model of a supercharged diesel engine chamber model is established and verified based on the ECFM-3Z combustion model. And the effects of different injection strategies on the in-cylinder combustion process at the altitude of 4550m are analyzed based on the verification of the plain bench test. The simulation results show that as the injection advance angle increases, the high temperature region in the cylinder shrinks when a single injection is used, the temperature distribution becomes uniform, the premixed combustion in the cylinder is enhanced. An increase in the fuel injection advance angle can reduce soot emissions but increase NOx emissions compared to the results under plain conditions. When using the multiple injection strategy, the advance of the pre-injection can make the fuel and air mix more fully, which helps the main injection fuel to burn better, the power can be further improved, but the average temperature inside the cylinder rises. However, due to the increase in the average internal temperature of the cylinder, the NOx emissions are increased compared with the single injection, and soot emissions are reduced. According to the simulation results, the injection strategy with the pre-ejection advance angle of 22°CA BTDC and the main spray advance angle of 2°CA BTDC is finally selected. The area of the indicator diagram is improved compared with the single injection, which can be restored to 85.6% of the plain.