Objective To explore the expression and clinical significance of β-arrestin1 in newly-diagnosed childhood acute lymphoblastic leukemia (ALL). Methods One hundred and fifty-five newly-diagnosed childhood ALL patients were enrolled in this study. Fifty-one sex- and age-matched patients without malignant hematological diseases were used as the control. The bone marrow samples were collected, then mononuclear cells of these samples were isolated. The mRNA expression of β-arrestin1 were detected by using quantitative real-time RT-PCR, and the protein expression were detected by western blot and immunofluorescence assays. The Spearman Correlation Coefficient was used to analyze the correlations between β-arrestin1 expression and ALL patients’s clinical and biological features. Results The expression of β-arrestin1 was significantly up-regulated in ALL patients compared with that in controls (P<0.01). β-arrestin1 expression was significantly higher in high risk (HR) group and medium risk (MR) group than that in standard risk (SR) group of ALL, as well as β-arrestin1 expression was higher in HR group than that in MR group. Moreover, β-arrestin1 expression was positively correlated with WBC count and risk classification of ALL with Spearman correlation analysis. Conclusion β-arrestin1 expression is correlated with the risk classfication of ALL, which could be a useful marker for the diagnosis, therapy strategy and prognosis.