Objective To explore the effect of multisensory intervention on the lactation in mothers of premature infants during the period of mother-infant separation, and to provide a reference for promoting the milk secretion of mothers of premature infants during this period. Methods A total of 88 mothers of premature infants were divided into a control group and an intervention group according to the admission time of premature infants, with 44 cases in each group. The control group was routinely given education on the knowledge and skills of breastfeeding, while the intervention group was subjected to multi-sensory interventions involving vision, hearing, smell and touch on the basis of routine nursing. The daily milk production within 7 days after delivery, the initiation time of the lactation period, the serum prolactin level and the breastfeeding situation within 42 days after delivery were compared between the two groups. Results A total of 41 cases in the intervention group and 39 cases in the control group completed the study. The milk production of the intervention group from 2 to 7 days after delivery was significantly better than that of the control group (all P<0.05). The initiation time of the lactogenesis Ⅱ , the prolactin level at 72 h postpartum and the exclusive breastfeeding rate within 42 days after delivery in the intervention group were significantly better than those in the control group (all P<0.05). Conclusion Multi-sensory interventions involving vision, hearing, smell and touch can increase early postpartum milk secretion of mothers of premature infants and improve exclusive breastfeeding rate of premature infants.