Various studies have recognized the vital role of the abnormal spindle microtubule assembly (ASPM) gene in the progression of numerous tumors and its association with their poorer clinical outcomes. Nonetheless, the clinical significance and regulatory mechanism of ASPM in papillary renal cell carcinoma (PRCC) have not been illuminated. Herein, we designed a series of experiments to determine the functional significance of ASPM in PRCC. The expression of ASPM was significantly elevated in PRCC tissues and cells, and a higher expression level of ASPM was associated with poor clinical outcomes in patients with PRCC. Following the knockdown of ASPM, the proliferation, invasion, and migration abilities of PRCC cells were all repressed. Moreover, the silencing of ASPM attenuated the expressions of crucial proteins involved in Wnt/b-catenin signaling pathway, including Dvl-2, β-catenin, TCF4, and LEF1. Our study shows the biological significance of ASPM in PRCC and provides new insights for exploring therapeutic targets in PRCC.