Objective:To study the clinical values of detection for SPOCK2 protein in serums of preterm infants and to determine a novel risk factor and therapeutic target against serious lung injuries of premature neonates. Methods:Upon diagnostic criteria of Respiratory Distress Syndrome(RDS),premature infants were divided into Group RDS(17 cases)and control(21 cases without RDS). ELISA and Western blot were performed to investigate the serum levels of SPOCK2 protein in every groups and expressions of SPOCK2 in human lung fibroblasts,respectively. The noncoding region in 3 terminal of SPOCK2 gene was analyzed to scan candidate binding sites of microRNA with software TargetScan online and followed verification was performed by fluorescence real-time quantification PCR. Person method was used to analyze the correlation between SPOCK2 and microRNA. The lentiviral vector of mir-124-3p was constructed and transfected into human lung fibroblasts. The regulatory effect of mir-124-3p on SPOCK2 expression was studied by Western blotting. Results:The serum levels of SPOCK2 protein in Group RDS were 16.43 ± 0.54 μg/L,which was higher than that of control(7.24 ± 0.43 μg/L,t=12.81,P < 0.01). There were several microRNAs located in the 3 terminal of SPOCK2 gene,including mir-124-3p,mir-25-3p,and mir-122-5p. However,mir-25-3p and mir-122-5p failed to be observed in serums of preterm infants. The expression of mir-124-3p was negatively correlative with that of SPOCK2 protein in preterm infants with lung injury(r=-0.645 9,P=0.012 6). Mir-124-3p overexpression markedly suppressed the expression of SPOCK2 protein in human fibroblasts. Conclusion:The detection of SPOCK2 protein in serum benefitted evaluating severity of preterm infants with RDS. Mir-124-3p down-regulated the expression of SPOCK2 protein,which might be helpful to build a novel therapeutic strategy against lung injury of premature neonates.