Experimental study on the effects of supercharging system, combustion chamber and injector, as well as EGR on combustion process, performance and emissions, was conducted on a common-rail heavy-duty (HD) diesel engine. Results show that the two-stage turbocharger (2 TC) can obviously enhance EGR recyclability and improve the trade-off relationships of NOx-soot and NOx-BSFC as compared to the single-stage turbocharger at low to middle speed and high load conditions. Soot, BSFC and the maximum in-cylinder pressure can be decreased by properly reducing compression ratio, optimizing structure parameters of combustion chamber (reentrant diameter and bowl depth) as well as using the injectors with taper holes. Experimental study on China Stage 4 of diesel engine with EGR technology was performed. Results of ESC cycle test show that, with increasing power density, 2 TC is superior to single turbocharger in terms of emissions and fuel economy. All emissions can meet the limits of China Stage IV for the engine of 29.8 kW/L using 2 TC without any after-treatment device, and the weighted BSFC is only 3% higher than that of the original engine. Thus, 2 TC is more suitable for HD diesel engine with high power density to achieve China Stage IV without after-treatment system.