Objective To investigate the effect of sleep position guidance on deformational plagiocephaly and/or brachycephaly (DPB) in the prematures. Methods 321 preterm infants in neonatal intensive care unit from October, 2012 to September, 2015 were divided into sleep positions guidance group (n=159) and control group (n=162). The sleep positions guidance group accepted sleeping positions guidance when they were in neonatal intensive care unit and followed up in child care clinic, and the control group accepted routine treatment and nursing. The incidences of DPB were compared. Results The incidences of mild (χ2=6.591, P=0.010), moderate (χ2=4.862, P=0.027) and severe (χ2=11.261, P=0.001) DPB were less in the sleep positions guidance group than in the control group. Conclusion Sleeping positions guidance may reduce the incidence of DPB in prematures.