Rapid and sensitive detection of the common acute lymphoblastic leukemia antigen (CD10) is crucial for diagnosing and prognosing hematopoietic tumors and several carcinomas. In the present study, a label-free immunosensor for detecting CD10 by Quartz Crystal Microbalance (QCM) was developed. The detection system has a good selectivity based on the biospecific interactions between the CD10 antigen and antibody, and the sensitivity of the immunosensor was further improved for Au NPs not only carried more antibodies but also acted as mass enhancers. Experimental results confirmed that this developed method could be conveniently used for the detection of CD10 without labeling, and CD10 could be measured quantitatively in the concentration range from 1.0 × 10−8 to 1.0 × 10−11 M.