Abstract: Objective To analyze the correlation of the mutations of exon 4 of pulmonary surfactant protein (SP)-B and SP-C with respiratory distress syndrome (RDS) in Mongolian premature infants. Methods Fifty cases of hospitalized genetically unrelated Mongolian premature infants with RDS (31 males, 19 females) were recruited as RDS group. In the same period, 50 cases (27 males, 23 females) of non RDS genetically unrelated premature infants of same ethnicity were choose as the control group. PCR and gene detection were used to detect exon4 of SP-B and SP-C genes. The differences of the genovariation and genotype frequency of 1580 locus in exon4 in SP-B, and of c.571C?>?A (T138N) locus in exon4 in SP-C were compared between two groups. Results The genovariation of 1580 locus in exon4 in SP-B was detected in 14 cases (with aberration rate of 28%) in RDS group and in 11 cases (with aberration rate of 22%) in control group, and the difference is not significant between two groups (χ2=0.480, P?>?0.05). The genotype frequency of CC, TT and CT gene in 1580 locus were 16%, 72%, and 12% respectively in RDS group; and 10%, 78%, and 12% respectively in control group. Meanwhile, the C and T gene frequency was 22% and 78% respectively in RDS group, and 16% and 84% in control group. There was no significant difference in genotype frequency between two groups (χ2=1.170, P?>?0.05). The genovariation of c.571C?>?A (T138N) locus in exon4 in SP-C was detected in 41 cases (with aberration rate of 82%) in RDS group and in 6 cases (with aberration rate of 12%) in control  group, and the difference is significant between the two groups (χ2=49.177, P??A (T138N) locus were 18%, 50%, and 32% respectively in RDS group; and 88%, 8%, and 4% in control group. Meanwhile, the C and A gene frequency was 34% and 66% respectively in RDS group, and 90% and 10% in control group. There was a significant difference in A gene frequency between the two groups (χ2=66.553, P??A (T138N) locus in exon4 in SP-C gene were in a higher risk of RDS. The mutation of 1580 locus in exon4 in SP-B had no correlation with Mongolian premature RDS.