Background: Multi-agent chemotherapy is the primary treatment for acute lymphoblastic leukemia (ALL), of which the asparaginase including Escherichia coli L-asparaginase (E. coli L-Asp) and Pegylated-asparaginase (PEG-Asp) is a cornerstone component. The study aimed to conduct a meta-analysis to compare the efficacy and safety of PEG-Asp with E. coli L-Asp in Chinese children with ALL. Methods: A systematic literature search was conducted to collect randomized controlled trials (RCTs) on PEG-Asp versus E. coli L-Asp in Chinese children with ALL. Two reviewers independently selected articles and extracted data. Risk-of-bias assessment used the Cochrane recommendation tool. Pooled estimates and risk ratios with 95% confidence intervals (CIs) for all outcomes in Review Manager 5.3. Results: 15 studies of a total of 470 publications were included, involving 1 194 patients. Pooled estimates showed that there were no significant differences in CR, ORR, gastrointestinal symptoms, and coagulation abnormalities rate between the PEG-Asp and E. coli L-Asp group (all P>0.05). Hypersensitivity (RR=0.63; 95%CI 0.40-1.01; Ρ=0.05) and hepatic injury rate (RR=0.45; 95%CI 0.27-0.75; Ρ=0.002) were lower in the PEG-Asp group. The frequency of administration and length of hospital stay of patients in the PEG-Asp group was less than that in the E. coli L-Asp group (both Ρ<0.0001). Conclusions: Current evidence pointed out a similarity efficacy in the two groups. While the PEG-Asp group had a lower hypersensitivity and hepatic injury rate. Besides, using PEG-Asp decreased the frequency of administration and the length of hospital stay, which, to some extent, might reduce patients’ burden caused by medical resources consumption.