Dry-cured meat products are considerably popular around the world due to unique flavor. Proteolysis is one of the enzymatic reactions from which flavor substances are derived, which is affected by endogenous proteases. The purpose aimed to reveal the potential relationship between endogenous proteases and key flavor substances in dry-cured pork coppa in this paper. The dynamic changes of endogenous proteases activity, free amino acids, and volatiles during dry-cured pork coppa processing were characterized. The results showed that 5 kinds of free amino acids, Glu, Lys, Val, Ala, and Leu, were identified as significant contributors to taste. Meanwhile, key volatiles, such as hexanal, nonanal, octanal, benzaldehyde, 3-methyl butanoic acid, 2-methyl propanoic acid, and ethyl octanoate, greatly contributed to the flavor characteristics of dry-cured pork coppa. Further partial correlation analysis was performed to better elucidate the relationship among parameters. The results revealed that close relationship between endogenous proteases and key substances. RAP not only significantly affected the accumulation of key active-amino acids, but also affected the accumulation of ethyl octanoate, 2,3-pentanedione, and 2,3-octanedione by regulating the accumulation of octanoic acid and Leu. In addition, cathepsin B and D, DPP II, DPP IV and RAP notably affected accumulation of hexanal.