Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a complex chronic inflammatory respiratory disease with multiple pathogenic factors and high morbidity and mortality. Serum levels of nuclear factor-kappa B (NF-kappa B), hypoxia-inducible factor-1 alpha (HIF-1 alpha), and surfactant protein D (SPD) were investigated in OSAHS patients, to determine their clinical significance and correlation with the pathogenesis. Patients were classified into a mild and moderate OSAHS group (n = 25) and severe OSAHS group (n = 33). Twenty healthy patients served as a control group. Peripheral blood levels of NF-kappa B, HIF-1 alpha, and SPD were determined by Western blot, and a correlation analysis was performed. Severe OSAHS patients received nasal continuous positive airway pressure (nCPAP) therapy and were followed up after 2 months. NF-kappa B p65, HIF-1 alpha, and SPD expression levels were determined after valid nCPAP therapy. NF-kappa B p65 and HIF-1 alpha expression was significantly higher in severe OSAHS group than in the other two groups (p < 0.01), and was positively correlated with the apnea-hypopnea index (AHI) (r = 0.696, p < 0.001; r = 0.634, p < 0.001). SPD expression was significantly lower in severe OSAHS group than in the control group (p < 0.01) and mild and moderate OSAHS group (p < 0.01), and was negatively correlated with AHI (r = -0.569, p < 0.001). OSAHS pathogenesis was associated with changes in NF-kappa B, HIF-1 alpha, and SPD protein expression levels. nCPAP therapy could improve the clinical characteristics of the patients, lower serum NF-kappa B and HIF-1 alpha levels, and increase serum SPD levels. We conclude that OSAHS is related to the expression of NF-kappa B, HIF-1, and SPD.