ABSTRACT Wilms’ tumor (WT) is a most common renal cancer that occurs among children, and microRNA‐19b (miR‐19b) usually participates in various human cancers. Importantly, the PTEN/PI3K/Akt signaling pathway plays a key role in cell apoptosis, growth and proliferation. Thus, our present study aims to investigate the effect of miR‐19b on the PTEN/PI3K/Akt signaling pathway during WT cell proliferation, migration, and apoptosis. WT tissues and adjacent normal tissues from WT patients were collected. qRT‐PCR was applied to detect miR‐19b expression in both the WT tissues and the adjacent normal tissues, immunohistochemistry was applied to detect the protein expressions of PTEN, P13K, and p‐Akt, SK‐NEP‐1 cells were divided into the blank, negative control (NC), miR‐19b mimics and miR‐19b inhibitors groups. MTT assay, propidium iodide (PI) staining, Annexin‐V/PI double‐staining, Transwell assay and Western blotting were performed to examine cell proliferation, cycle, apoptosis, migration, and invasion, and the protein expressions of PTEN, P13K, Akt, and p‐Akt. Increased miR‐19b expression, positive expression rates of P13K and Akt, decreased PTEN expression rate, a negative correlation between PTEN expression and tumor lymph node metastasis, and a positive correlation between the expression of P13K and Akt and the clinical stages were observed in the WT tissues. The miR‐19b inhibitors group exhibited decreased cell proliferation, cell cycle progression, migration and invasion, and protein expressions of PI3K and p‐Akt but increased PTEN protein expression compared with the blank and NC groups. Thus, inhibition of miR‐19b suppresses the progression of WT by modulating the PTEN/PI3K/AKT signaling pathway. J. Cell. Biochem. 118: 3424–3434, 2017. © 2017 Wiley Periodicals, Inc.