ObjectiveTo systematically evaluate the efficacy and safety of nucleo(s)tide analogues (NAs) sequential/NAs sequential combined with pegylated interferon (PegIFN) for the treatment of HBeAgpositive chronic hepatitis B（CHB）. MethodsPubMed, Cochrane Library, Embase, and Chinese Medical databases (CNKI, Wanfang and VIP) from database establishment to March 25, 2017 were retrieved, randomized controlled trials of NAs sequential/sequential combined with PegIFN for the treatment of CHB after application of NAs to achieve virologic response were included in study, Meta analysis was performed by RevMan 5.3 software, HBeAg seroconversion rate and HBsAg negative conversion rate at the end of treatment were compared. ResultsNine studies were eventually included, 4 were about NAs sequential PegIFN,5 about NAs sequential combined with PegIFN. At the end of treatment, compared with using NAs monotherapy for antiviral treatment, NAs sequential/sequential combined with PegIFN therapy can improve HBeAg seroconversion rate(31.2％ vs 11.7％；OR, 3.69 ［95％CI, 2.43-5.60］；P＜0.01) and HBsAg negative conversion rate(11.5％ vs 0.5％；OR, 9.31［95％CI, 2.72-31.89］；P＜0.01). According to the results of subgroup analysis, HBeAg seroconversion rate in NAs sequential PegIFN therapy group was higher than control group (25.3％［42/166］ vs 10.0％［17/170］; OR,3.1［95％CI, 1.66-5.79］；P＜0.01)；HBeAg seroconversion rate in NAs sequential combined with PegIFN therapy was higher than control group (36.8％［63/171］ vs 13.5％［23/171］；OR,4.24［95％CI, 2.41-7.46］；P＜0.01). Sequential/sequential combination therapy showed more adverse reaction, most of which can be tolerated or improved after symptomatic treatment. ConclusionFor the treatment of HBeAgpositive CHB, after application of NAs to achieve virologic response, NAs sequential/sequential combined with PegIFN therapy for 48 weeks can significantly increase HBeAg seroconversion rate and HBsAg negative conversion rate.