Diesel engines operated at high altitudes would experience performance degradation due to the fuel-air amount mismatch, resulting in combustion deterioration. Technologies that supplement oxygen concentration, such as intake oxygen enrichment, turbocharging and the addition of oxygenated fuel additives, can help restore performance at high altitudes, but each has its own limitations Operating diesel engines at high altitudes still generates extremely lean fuel-air mixtures, making the improved utilization of excess air the most economically efficient approach to optimize engine performance under such conditions. The objective of this paper is to investigate the effects of injector nozzle-hole numbers on diesel engines operated at high altitudes, a topic that has been limitedly discussed in existing literature, with the aim of enhancing understanding regarding the potential of this cost-effective approach and aiding in the design of a cooperative approach between oxygen concentration supplementation techniques and better oxygen utilization techniques, ultimately optimizing engine performance at high altitudes. The results suggest that increasing the number of nozzle-holes enhances fuel-air mixing, leading to improved combustion quality and enhancing the engine’s adaptability to altitude. However, at extremely high altitudes, such as altitudes exceeding 3000 meters, configurations with a larger number of nozzle-holes still exhibit high concentrations of incomplete combustion products, such as soot emissions, in the exhaust. This reduced combustion efficiency is mainly attributed to the longer spray penetration length at high altitudes, which causes intensified spray impingement on the cavity wall, subsequently resulting in inefficient combustion of the fuel flowing into the squish zone during spray impingement. This inefficiency may be mitigated by optimizing the shape of the combustion chamber. It is worth noting that increasing the number of nozzle-holes can also lead to a higher pressure rise rate. Considering that high altitude operations already result in a higher pressure rise rate, further increasing the nozzle-hole number may exceed the allowable threshold and increase the likelihood of engine component failure. Consequently, the strength of engine components becomes a limiting factor when attempting to increase the number of nozzle-holes for improved engine altitude adaptation.