Abstract: Objective To explore the efficacy and safety of valaciclovir hydrochloride granules combined with stomatitis spray in the treatment of children with herpetic stomatitis. Methods A total of 150 children with herpetic stomatitis were selected and divided into control group A(n=50), control group B(n=50)and experimental group(n=50)according to the sealed envelope method. The control group A was treated with valaciclovir hydrochloride granules, the control group B was treaded with stomatitis spray, the experimental group was treated with valaciclovir hydrochloride granules and stomatitis spray, and all the children were treated for 1 week. The therapeutic effect, relief time of clinical symptoms(regression time of herpes, recovery time of body temperature, rehabilitation time), levels of serum inflammatory factors ［interleukin-10(IL-10), interleukin-2(IL-2), tumor necrosis factor-α(TNF-α)］, quality of life ［score of Infant Dermatology Quality of Life Index(IDQOL)］ and safety indicators ［result of blood test, adverse reactions］ were compared among the three groups. Results After treatment, the therapeutic effect in the experimental group was significantly better than that in the control group A and control group B(P<0.05). The regression time of herpes, recovery time of body temperature and rehabilitation time in the experimental group were significantly shorter than those in the control group A and control group B(P<0.05). After treatment, the level of IL-10 - increased significantly in the three groups, while levels of IL-2 and TNF-α decreased significantly (P<0.05), and changes of levels of IL-10, IL-2 and TNF-α in the experimental group were significantly greater than those in the control group A and the control group B(P<0.05). The IDQOL score in the three groups significantly decreased after treatment, and was significantly lower in the experimental group than that in the control group A and the control group B(P<0.05). There was no significant difference in the result of blood test among the three groups, and no obvious adverse reactions were observed. Conclusion Valaciclovir hydrochloride granules combined with stomatitis spray is effective in the treatment of children with herpetic stomatitis, which can shorten the relief time of clinical symptoms, improve the levels of serum inflammatory factors and the quality of life, and has higher safety.