To investigate clinical effectiveness of mupirocin and He-Ne laser radiation on neonatal omphalitis through the controlled study. 86 cases of neonatal omphalitis was selected from 2013 to 2018, divided into observation group (mupirocin + He-Ne laser therapy)and the control group (mupirocin)according to different treatments, with 43 cases in each group. Neonatal omphalitis healing time and adverse event was recorded .It was found that the average healing time of observation group was (4.186±0.194)d, the total effective rate was 100%, and average healing time was (5.189±0.238)d, the total effective rate was 86%on the control group. Healing time of observation group were significantly higher than that of control group (P<0.05). Adverse events such as skin rash were not found in two groups. Study shows that mupirocin combined with He-Ne laser radiation therapy for the treatment of neonatal omphalitis have good clinical curative effect, high safety.