AIM: To screen the active constituents in Taohong Siwu Decoction(THSWD) by Systems Pharmacology and to study its protective effect on myocardial injury through cell experiments.  METHODS: The TCMSP database and Pharmmaper database were used to retrieve the constituents and active constituent targets of THSWD. The Genecards database was used to retrieve the myocardial injury related targets gene. Then construct and analyze the constituents-disease intersection target network and the contribution value of constituents, and screen out the main active constituents of THSWD acting on the myocardium. Furthermore, CoCl2 was used to induce H9c2 to establish a hypoxic injury model, and the effects of the selected active constituents on cell viability were detected. The level of myocardial enzyme and energy metabolism were detected to investigate whether the active constituents in THSWD play a protective effect on myocardial injury by affecting energy metabolism. RESULTS: The screening found that THSWD contained 73 active constituents, which corresponded to 340 targets, while 1 544 disease targets related to myocardial injury. According to the network diagrams of constituents-disease intersection targets, quercetin, ferulic acid and paeoniflorin were screened out as the main active constituents of THSWD against myocardial injury. Further experiments found that ferulic acid can significantly increase the viability of H9c2 induced by CoCl2 (P<0.05), and significantly reduce the levels of CK, CK-MB and LDH after CoCl2 stimulation (P<0.01). In addition, ferulic acid can inhibit the increase of LD level and the decrease of ATP level after CoCl2 stimulation (P<0.01). CONCLUSION: Ferulic acid in THSWD is the main active constituent against myocardial injury and it can protect the myocardium by inhibiting myocardial enzyme levels and improving energy metabolism disorders.