Previous studies have reported excessive expression of apoptosis-antagonizing transcription factor (AATF) in various tumors, where it reinforces the generation and development of cancers and is linked to the clinical outcome. Nevertheless, the expression and influence of AATF in Wilms' tumor (WT) is largely unknown. Here, we discovered that AATF expression was markedly increased in WT tissues as compared to the surrounding normal tissues. Elevated levels of AATF expression were related to tumor relapse and pulmonary metastasis, congruent with it being a predictor of clinical outcome in people suffering from WT. Proliferation, invasion, and migration of WT cells were suppressed by knockdown of AATF and promoted by AATF overexpression in vitro. Furthermore, the tumor generation capability of WT cells noticeably decreased after knockout of AATF in vivo. The phosphoinositide-3-kinase (PI3K)/AKT pathway modulated the activity of AATF in WT. The findings of our study indicate that AATF expression is increased in WT and can serve as a predictor of clinical outcome; in addition, it may enhance the development of WT via the PI3K/AKT axis and may be a promising marker for WT diagnosis and therapy.