To explore the clinical significance of early oral intervention measures in the prognosis of premature infants. 151 preterm infants admitted to neonatal intensive care unit (NICU) of Liaocheng People's Hospital from January 2015 to January 2017 were enrolled. Premature infants were divided into intervention group and control group according to random number table method and with the consent of legal guardian. Both groups received routine treatment of preterm infants after stable vital signs. The intervention group received the oral massage method adopted by none-nutritive sucking, stimulating swallowing function and SandraFucile on the basis of routine treatment, once a day for 14 consecutive days. Both groups were followed up for 6 months. The oral feeding ability of premature infants was evaluated by the proficiency (PRO), rate of transfer (RT), feeding process and non-nutritive suction (NNS). At 40 weeks of postmenstrual age (PMA), neonatal behavioral neurological (NBNA) was used to assess neonatal brain development; Infanib was used for early motor development evaluation at 3 months and 6 months after birth. Finally, 151 premature infants were enrolled, including 78 in the intervention group and 73 in the control group. The time to complete oral feeding of the intervention group was significantly shorter than that of the control group (days: 18.1±3.7 vs. 23.4±5.8, P < 0.05). Compared with the control group, at the time of complete oral feeding, the PMA of the intervention group was significantly decreased (weeks: 33.4±0.9 vs. 35.9±1.9, P < 0.05), the feeding efficiency was significantly increased (mL/min: 10.6±5.1 vs. 8.1±4.7, P < 0.05), and PRO was significantly increased [(95±8)% vs. (72±28)%, P < 0.05], and the body weight was significantly decreased (g: 1 836.0±193.0 vs. 2 000.8±204.5, P < 0.05). The NNS scores of the intervention group and the control group were increased gradually with time (F values were 86.21 and 75.23, respectively, both P < 0.01), and the NNS scores of the intervention group at 10 days and 14 days were significantly higher than those of the control group (52.89±6.26 vs. 46.74±6.24, 73.90±7.01 vs. 63.53±6.80, both P < 0.01). The NBNA scores of the two groups were lower, but there was no significant difference between the intervention group and the control group (32.7±3.6 vs. 32.0±4.1, P > 0.05). Infanib evaluation at 3 months of age showed that the proportion of normal children in the intervention group was significantly higher than that in the control group [67.95% (53/78) vs. 49.31% (36/73), P < 0.05], and at 6 months of age, the proportion of normal children in the intervention group was significantly higher than that in the control group [84.62% (66/78) vs. 58.90% (43/73), P < 0.01]. Early oral exercise intervention can shorten the transition time from tube feeding to full oral feeding in NICU premature infants and improve the performance of infants during feeding.