Background <p>Up to 40% of adolescent and young adult cancer survivors (AYAs) experience anxiety after cancer treatment. Evidence from healthy controls suggests that the prefrontal cortex exerts a regulatory influence over the amygdala, facilitating reappraisal of fear-inducing stimuli and preventing maladaptive emotional responses. Increased anxiety severity has been associated with low amygdala–ventral medial prefrontal cortex (vmPFC) connectivity, but little is known about the neural correlates of anxiety in AYA cancer survivors. The purpose of this cross-sectional study was to explore the association between amygdala-vmPFC connectivity and anxiety severity among AYA cancer survivors.</p> Methods <p>Seventeen post-treatment AYA cancer survivors were recruited from the University of Michigan. Participants completed an anxiety self-report and a 45-minute functional MRI scan that consisted of resting and task-based conditions (i.e., viewing pleasant, neutral, or unpleasant scenes). General linear models were constructed to investigate the effect of self-reported anxiety on the functional connectivity between the amygdala and vmPFC regions.</p> Results <p>Anxiety severity was positively associated with the functional connectivity between the right amygdala and vmPFC (MNI: -2, 54, 14; <i>k</i> = 323 voxels; peak t-statistic = 9.16; peak beta = 0.34; <i>p</i> = 0.04) while viewing pleasant images, but not other images or during rest. Analyses using the left amygdala as a seed region did not yield significant correlations.</p> Conclusions <p>The positive association between anxiety severity and amygdala-vmPFC connectivity while viewing positive stimuli may suggest an overly active neural pathway linked to overall ineffective emotional regulation. Further understanding of amygdala-vmPFC connectivity as a potential mechanism underlying anxiety may provide evidence toward a viable target for intervention research.</p>