The purpose of this paper is to explore the distribution of in-cylinder exergy destruction and its influence factors in combustion process. A heavy-duty turbocharged diesel engine is taken as the research object to study exergy change rule, exergy destruction distribution in cylinder and its influence factors based on test platform, STAR-CD computational fluid dynamics software and subsequent theoretical calculation. The results show that first, exergy destruction in cylinder mainly happens in combustion process, the exergy destruction caused by chemical reaction and its proportion to in-cylinder exergy destruction are positively related with engine load at the same speed, the proportion is up to 94.5% at B75 working condition. Secondly, exergy destruction in cylinder of diesel engine is mainly caused by chemical reaction irreversibility and it mostly occurs at the edge of oil beam. Third, the largest chemical reaction exergy destruction rate happens in dense mixing zone whose equivalence ratio range is 1~1.5; however, the value is relatively low in dilute mixing region or denser mixing zone whose equivalence ratio is lower than 1 or greater than 1.5. With the development of combustion process, the reaction exergy destruction rate decreases gradually in different equivalence ratios zone. Fourth, in a certain temperature range, the chemical reaction exergy destruction rate is almost proportional to the heat release rate of fuel, and in a certain heat release rate region, the chemical reaction exergy destruction and its proportion of the fuel exergy gradually reduces with the temperature increase. Finally, as the combustion process proceeding, the relative intensity of equivalence ratio, temperature and chemical reaction exergy destruction decrease gradually.