Autism spectrum disorder (ASD) is typically characterized by impairments in social interaction and communication, which may be associated with a failure to naturally orient to social stimuli, particularly in recognizing and responding to facial emotions. As most previous studies have used nonsocial stimuli to investigate inhibitory control in children and adults with ASD, little is known about the behavioral and neural activation patterns of emotional inhibitory control in adolescent with ASD. Functional neuroimaging studies have underscored the key role of the prefrontal cortex (PFC) in inhibitory control and emotional face processing. Thus, this study aimed to examine whether adolescent with ASD exhibited altered PFC processing during an emotional Flanker task by using non-invasive functional near-infrared spectroscopy (fNIRS). Twenty-one adolescents with high-functioning ASD and 26 typically developing (TD) adolescents aged 13–16 years were recruited. All participants underwent an emotional Flanker task, which required to decide whether the centrally positioned facial emotion is consistent with the laterally positioned facial emotion. TD adolescents exhibited larger RT and mean O2Hb level in the incongruent condition than the congruent condition, evoking cortical activations primarily in right PFC regions in response to the emotional Flanker effect. In contrast, ASD adolescents failed to exhibit the processing advantage for congruent versus incongruent emotional face in terms of RT, but showed cortical activations primarily in left PFC regions in response to the emotional Flanker effect. These findings suggest that adolescents with ASD rely on different neural strategies to mobilize PFC neural resources to address the difficulties they experience when inhibiting the emotional face.