Acute lung injury (ALI) is an acute inflammatory disorder. Toll-like receptor-4 (TLR-4) and Stanniocalcin -1 (STC-1) had roles in lung endothelial protection. This study aims to assess TLR-4 and SCT-1 genes expressions in peripheral blood of ALI patients. Total RNA was extracted from peripheral blood of 48 subjects (20 healthy controls, 28 ALI patients) and expressions of genes were assessed by real-Time qRT-PCR. The expression levels of TLR-4 and SCT-1 genes were significantly lower in ALI patients compared to controls (P < 0.0001). After 10 days, the expression levels of TLR-4 and SCT-1 were increased compared to their baseline levels (p=0.012 and 0.024, respectively). SCT-1 has 92.9% sensitivity and 100% specificity in ALI detection. SCT-1 gene expression was negatively correlated with severity score (r= −0.54, p=0.003). The mortality pattern was higher in ALI patients with lower TLR-4 gene expression (p=0.014). In conclusion, the peripheral blood expressions of TLR-4 and STC-1 genes were decreased in ALI patients. Both genes expressions were increased with patients' recovery. SCT-1 had higher sensitivity and specificity in ALI diagnosis. The peripheral blood expressions of SCT-1 and TLR- 4 genes seem to be diagnostic and prognostic markers in ALI.