Objective To explore the clinical significance of combined detection of homocysteine (Hcy) and myocardial enzyme spectrum in premature infants with asphyxia ,and provide scientific basis for differential diagnosis and treatment of hyperbilirubi‐nemia in premature infants .Methods A total of 150 cases of premature infants with hyperbilirubinemia hospitalized in this hospital from January 2011 to May 2014 were selected and divided into the mild asphyxia group and server asphyxia group .Other 100 cases of premature infants with physiologic jaundice were selected as the control group .Serum levels of total bilirubin(TBIL) ,homocys‐teine(Hcy) and indicators of myocardial enzyme spectrum were detected and comparatively analysed .Results The levels of TBIL , Hcy and indicators of myocardial enzyme spectrum in the mild asphyxia group and server asphyxia group were higher than those in the control group ,had statistically significant differences(P<0 .05) .Combined with the clinical data and the detection results of col‐or Doppler ultrasound ,3 cases of premature infants with asphyxia complicated with hyperbilirubinemia were diagnosed as myocardi‐tis ,29 cases were diagnosed as subclinical myocarditis and 46 cases were diagnosed as suspected myocarditis .Conclusion Different degrees of myocardial cell damage exists in premature infants with hyperbilirubinemia ,and routine determination of Hcy and myo‐cardial enzyme spectrum have positive significance for clinical diagnosis of neonatal myocarditis and subclinical myocarditis .