Byline: Hui-Juan Cao, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing; Shi-Bing Liang, Shanxi University of Chinese Medicine, Taiyuan, Shanxi Province; Wei Zhou, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing; Jia-Rui Wu, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing; Cheng-Liang Zhang, Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China. Abstract BACKGROUND:: To systematically evaluate the effect and safety of Xing Nao Jing (XNJ) injection as an add-on treatment on the treatment for viral encephalitis (VE). METHODS:: Trials assessing the adjunctive effectiveness of XNJ injection for VE were searched from 4 electronic databases from inception to October 31, 2018. Two authors independently extracted data and assessed risk of bias. Statistical analyses were performed using RevMan 5.3 software. Meta-analysis and additional analysis were conducted if data permitted. Trial Sequential Analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were also performed. RESULTS:: This review involved 23 trials and 1757 participants, all trials were assessed as having unclear risk of bias. Results from 5 meta-analyses, 13 subgroup meta-analyses, and the single studies showed that based on conventional therapy XNJ injection (0.4-0.6 mL/kg daily for children, 20 mL/day for adults) may have better effect on increasing the numbers of cured patients and decreasing the time of recovery of main symptoms for patients with viral encephalitis. Patients used combination of XNJ injection and conventional therapy had higher cured rate (risk ratio 1.61, 95% confidence interval 1.45-1.80, 19 trials, 1456 participants) and less mortality rate (risk ratio 0.26, 95% confidence interval 0.10-0.71, 9 trials, 595 participants). The average difference of time for fever, conscious, or convulsive recovery was average 2 hours shorter in combination group than in control. No difference was found between children and adults according to the subgroup analysis. Safety of the XNJ injection was failed to evaluate due to the insufficient evidence in this review. CONCLUSIONS:: This review found "very low" quality evidence which showed the potential effectiveness of combination of XNJ injection and conventional therapies for VE. Considering the TSA results, conclusion could only be draw on effectiveness of the XNJ injection as add-on treatment for VE patients on increasing the cured rate. Firm conclusion on other outcome measures for effectiveness assessment or safety of XNJ injection could not be draw according to this review due to the insufficient evidence.