Background: Adolescents with bipolar disorder (BD) are often misdiagnosed with major depressive disorder (MDD), which delays the introduction of appropriate treatment resulting in adverse outcomes. This study examined the psychometric properties of the 33-item Hypomania Checklist (HCL-33) and its accuracy to distinguish BD from MDD in adolescents. Method: A total of 248 participants (171 MDD and 77 BD patients) were recruited from a university-affiliated hospital in China. Depression was measured with the Hamilton Depression Rating Scale. All participants completed the assessment with the HCL-33. Results: A two-factor structure was found for the HCL-33, which explained 30.2% of the total variance. The internal consistency and split half reliability of the total scale were acceptable. The optimal cut-off value of 18 generated sensitivity of 0.52 and specificity of 0.73 for distinguishing BD from MDD. Conclusion: The HCL-33 seems to be a useful screening instrument to distinguish BD from depressed adolescents. However, considering certain less than robust psychometric properties, the HCL-33 needs to be modified and further refined for adolescent patients.