Environment enrichment (EE) has a variety of effects on brain structure and function. Brain-derived neurotrophic factor (BDNF) is essential for EE-induced hippocampal neurogenesis and memory enhancement. However, the intracellular pathway downstream of BDNF to modulate EE effects is poorly understood. Here we show that integrin-linked kinase (ILK) levels are elevated upon EE stimuli in a BDNF-dependent manner. Using ILK-shRNA (siILK) lentivirus, we demonstrate that knockdown of ILK impairs EE-promoted hippocampal neurogenesis and memory by increasing glycogen synthase kinase-3β (GSK3β) activity. Finally, overexpressing ILK in the hippocampus could rescue the neurogenesis and memory deficits in BDNF(+/-) mice. These results indicate that ILK is indispensable for BDNF-mediated hippocampal neurogenesis and memory enhancement upon EE stimuli via regulating GSK3β activity. This is a new insight of the precise mechanism in EE-enhanced memory processes and ILK is a potentially important therapeutic target that merits further study.