Objective: To explore the pathogenesis, clinicopathological characteristics neonatal hyaline membrane disease (NHMD), improves the cognition of NHMD, and increase diagnosis level. Methods: Retrospective analysis underwent in 12 NHMD cases of clinical and pathological data in the Pathology Department of Affiliated Hospital of Zunyi Medical College from January 2009 to December 2015. Results: There were 3 cases of female and 9 cases of male in 12 cases NHMD; survival period was ranging from 8 hours to 3 days; the 12 cases including 9 cases of premature infants, 3 cases of cesarean section. All 12 cases were in good condition when they were born. In 6 hours after birth, they presented with progressive dyspnea, cyanosis, breath groan, and eventually died of respiratory failure. The pathological changes indicated a alveolar, end bronchial capillary wall with a layer of transparent uniform structure or granular eosinophilic membrane attachment. Conclusion: NHMD was usually occured in premature infant, pathogenesis not only is the deficiency of pulmonary surfactant, but also it is believed to free radical generation and oxidative stress in the inflammatory process, while it is extremely important to strengthen the maternal health care and raise awareness of the disease in order to reduce the neonatal mortality and medical disputes.