Objective To analyze the clinical effect of caffeine citrate on apnea and its effect on endothelin, nitric oxide and β-endorphin in premature infants. Methods 118 children with apnea-hypoprenalia were selected and divided into experimental group and control group according to different treatment methods. The control group were treated with aminophylline, and the experimental group were treated with caffeine citrate. The clinical symptoms, endotheliolysin, nitric oxide and β-endorphin in two groups of patients were compared. Results The total effective rate of 84.75% (50/59) in the experimental group was higher than 69.49% (41/59) in the control group(P<0.05). The incidence of abdominal distension, heart rate, feeding intolerance, bronchopulmonary dysplasia and irritability were significantly lower in the experimental group than those in the control group (P <0.05) . After treatment, the levels of endotheliolysin, nitric oxide in the experimental group were significantly higher than those in the control group (P <0.05), and the level of β endorphin in the experimental group was significantly lower than that in the control group (P <0.05). Conclusion Caffeine citrate has a significant clinical effect on apnea in premature infants, and can reduce the incidence of adverse reactions.