Abstract: Objective To investigate the changes of peripheral blood cystatin C (Cys C) in premature infants and its clinical significance. Methods A total of 89 premature infants who were admitted into Department of Neonates, the Affiliated Hospital of Xuzhou Medical University from January to June 2018 were enrolled, including 47 boys and 52 girls, with an average gestational age of (32.78 ±2.26) weeks and an average body weight of (1.94 ±0.48) kg. The level of Cys C in peripheral blood was measured by particle enhanced transmission immunoturbidimetry. SPSS 18.0 software was used to compare the difference of Cys C level in different gestational ages, gender, birth weight, mode of production, Apgar score, pregnancy induced hypertension and premature rupture of membranes, and to analyze the relationship between Cys C and gestational age, birth weight, Apgar score, creatinine (CR), blood urea nitrogen (BUN), and total bilirubin (TBIL). Results The level of Cys C was remarkably higher in early preterm infants than those in middle and late preterm infants (P<0.05), while no significant difference was found between middle and late preterm infants (P>0.05). The Cys C level of premature infants with very low birth weight was higher than those with low and normal birth weight (P<0.05), but there was no significant difference between premature infants with low and normal birth weight (P>0.05). The level of Cys C in preterm infants with 5-min Apgar score<8 was significantly higher than that in preterm infants with 5-min Apgar score > 8 (P<0.05). The level of Cys C in preterm infants with premature rupture of membranes was higher than that in preterm infants without premature rupture of membranes (P<0.05). There was no significant difference in Cys C among different genders, modes of production, TBIL levels and mothers with or without pregnancy induced hypertension (P>0.05). According to correlation analysis, Cys C level was positively correlated with creatinine and urea nitrogen (P<0.05); negatively correlated with gestational age, birth weight and Apgar scores (P<0.05), without close relationship (r<0.5); with no correlation with TBIL (P>0.05). Conclusions Gestational age, birth weight, 5-min Apgar score and premature rupture of membranes are the influence factors of Cys C level of preterm infants. The smaller the gestational age and the lower the birth weight and 5-min Apgar score, the higher the Cys C level of preterm infants, with a negative correlation. For such preterm infants, we should be highly aware of the presence of renal injury. However, gender, mode of production, TBIL level and pregnancy-induced hypertension produce no significant effect on Cys C level.