Objective To study the clinical efficacy of Er: YAG laser in combination with periodontal treatment of chronic periodontitis and its effect on cytokines in gingival crevicular fluid. Methods 120 cases of chronic periodontitis patients admitted to the Second Hospital of Shijiazhuang City from August 2016 to July 2017 were selected as the subjects of this study. All the patients according to random number table method is divided into traditional medicine group and laser group, each group of 60 cases. The patients in the Traditional medicine group were given conventional periodontal basis of treatment, and the patients in the Laser group patients were given Er: YAG laser combined with periodontal for treatment. The clinical indicators of periodontal before and after treatment and the changes of cytokine levels in gingival crevicular fluid in both groups were observed and compared. Results Before the treatment, there was no significant difference in periodontal clinical parameters between the two groups. After treatment, the levels of periodontal clinical parameters (BI, PD, CAL) in both groups were lower than those before treatment, and the laser group was lower than the traditional group. The difference was statistically significant. The levels of cytokines (IL-6, IL-8, TNF-α) in gingival crevicular fluid before treatment in both groups showed no significant difference. After treatment, the levels of IL-6, IL-8 and TNF-α in both groups were lower than those before treatment, and the difference between the two groups was statistically significant. Conclusion Er: YAG laser combined with periodontal treatment of chronic periodontitis significant clinical efficacy, can effectively reduce the patient’s periodontal inflammatory response to improve the patient’s gingival bleeding, deserved clinical promotion.