This study investigates the expression of phosphatase and tensin homolog (PTEN) and Inositol polyphosphate 4-phosphatase type II (INPP4B) in children with acute myeloid leukemia. The levels of PTEN and INPP4B in bone marrow, from 95 acute myelogenous leukemia (AML) patients and 84 controls, respectively, were assessed by immunohistochemistry, quantitative polymerase chain reaction (qPCR), and Western blot. The prognosis was followed up and investigated and the correlation analysis was made. We found that the expression levels of PTEN and INPP4B were significantly lower in the AML group than those in the control group (P < 0.05). The survival time was lower in PTEN and INPP4B negative children relative to PTEN and INPP4B positive children (P < 0.05). In AML patients, INPP4B and PTEN expression was positively correlated (r = 0.552, P = 0.000). In conclusion, the levels of INPP4B and PTEN were reduced significantly and correlated positively in AML patients accompanying with abnormal karyotypes. The current investigation of INPP4B and PTEN could give new insight into targeted therapy for AML.