Objective To investigate the effect of Huangqi injection on the short-term prognosis in childhood with acute lymphoblastic leukemia (ALL). Methods A retrospective analysis was performed on the clinical data of 105 children newly diagnosed with ALL between January 2009 and December 2012. These children were randomly divided into treatment group (18 low-risk cases, 7 medium-risk cases, and 24 high-risk cases) and control group (21 low-risk cases, 7 medium-risk cases, 28 high-risk cases). Both groups were given remission induction therapy based on the levels of risk. Throughout the remission induction therapy, the treatment group also received Huangqi injection (0.5-1.0 mL/kg per day) by intravenous infusion, while the control group was given 0.9% sodium chloride injection instead. The two groups were compared in terms of distribution of prognostic factors and complete remission (CR) rate after remission induction therapy, as well as the incidence of minimal residual disease (MDR) (≥ 10^-4 and < 10^-4) among all patients in the two groups on day 19 of remission induction therapy and among B-ALL patients in the two groups when achieving a CR at the end of remission induction therapy. Results Of the 105 children with ALL, 99 had B-ALL, and 6 had T-ALL. There were no significant differences in the distribution of prognostic factors between the two groups (P>0.05). The overall CR rate of 105 patients was 79%; there was no significant difference in CR rate between the treatment and control groups (82% vs 77%; P>0.05); also, no significant differences were found between the two groups in the CR rates among high-, medium-, and low-risk cases (P>0.05). On day 19 of remission induction therapy, the incidence of MRD ≥10^-4 in the treatment group was significantly lower than that in the control group (69% vs 95%; P<0.05); among 80 children with B-ALL who achieved a CR (43 cases in the control group and 37 cases in the treatment group), the incidence of MRD ≥10^-4 was significantly lower in the treatment group than in the control group (27% vs 58%; P<0.05); in both circumstances above, the high-and low-risk cases in the treatment group had a significantly lower incidence of MRD ≥10^-4 than the control group (P<0.05). Conclusions Huangqi injection combined with chemotherapy has an enhanced anti-tumor effect and can improve the short-term prognosis and clinical outcome in children with ALL.