AimPancreatic cancer (PC) has a poor prognosis and high mortality. Kruppel‐like factor 9 (KLF9), a transcription factor, is aberrantly expressed in various neoplasms. The current study sought to analyze the functional role of KLF9 in the proliferation, invasion, and migration of PC cells.MethodsThe expression patterns of KLF9 and KIAA1522 in normal pancreatic cells (HPDE‐C7) and PC cells (Panc 03.27, BxPc3, SW1990) were determined by real‐time quantitative polymerase chain reaction and Western blot assay. After treatment of KLF9 overexpression, proliferation, invasion, and migration were evaluated by cell counting kit‐8, 5‐ethynyl‐2′‐deoxyuridine staining, and Transwell assays. The binding of KLF9 to the KIAA1522 promoter was analyzed by dual‐luciferase assay and chromatin immunoprecipitation. The rescue experiment was conducted to analyze the role of KIAA1522.ResultsKLF9 was downregulated, while KIAA1522 was upregulated in PC cells. KLF9 overexpression mitigated the proliferation, invasion, and migration of PC cells. Enrichment of KLF9 led to inhibition of the KIAA1522 promoter and repressed KIAA1522 expression. KIAA1522 overexpression neutralized the inhibitory role of KLF9 in PC cell functions.ConclusionKLF9 is enriched in the KIAA1522 promoter and negatively regulates KIAA1522 expression, thereby mitigating the proliferation, invasion, and migration of PC cells.