Background: In the clinical setting, a large proportion of children with an autism spectrum disorder (ASD) experience anxiety symptoms. Because anxiety is an important cause of impairment for children with an ASD, it is necessary that effective anxiety interventions are implemented for these children. Recently, a serious game called Mindlight has been developed that is focused on decreasing anxiety in children. This approach is based on recent research suggesting that video games might be suitable as an intervention vehicle to enhance mental health in children. In the present study it will be investigated whether Mindlight is effective in decreasing (sub) clinical anxiety symptoms in children who are diagnosed with an ASD. Methods/Design: The present study involves a randomized controlled trial (RCT) with two conditions (experimental versus control), in which it is investigated whether Mindlight is effective in decreasing (sub) clinical anxiety symptoms in children with an ASD. For this study, children of 8-16 years old with a diagnosis of an ASD and (sub) clinical anxiety symptoms will be randomly assigned to the experimental (N = 60) or the control (N = 60) condition. Children in the experimental condition will play Mindlight for one hour per week, for six consecutive weeks. Children in the control condition will play the puzzle game Triple Town, also for one hour per week and for six consecutive weeks. All children will complete assessments at baseline, post-intervention and 3-months follow-up. Furthermore, parents and teachers will also complete assessments at the same time points. The primary outcome will be child report of anxiety symptoms. Secondary outcomes will be parent report of child anxiety, child/parent report of depressive symptoms, and parent/teacher report of social functioning and behavior problems. Discussion: This paper aims to describe a study that will examine the effect of the serious game Mindlight on (sub) clinical anxiety symptoms of children with an ASD in the age of 8-16 years old. It is expected that children in the experimental condition will show lower levels of anxiety symptoms at 3-months follow-up, compared to children in the control condition. If Mindlight turns out to be effective, it could be an important contribution to the already existing interventions for anxiety in children with an ASD. Mindlight could then be implemented as an evidence-based treatment for anxiety symptoms in children with an ASD in mental health institutes and special education schools.