Background: Preventive interventions are developed for children of parents with mental and substance use disorders (COPMI), because these children have a higher risk of developing a psychological or behavioral disorder in the future. Mental health and substance use disorders contribute significantly to the global burden of disease. Although the exact number of parents with a mental illness is unclear, the subject of mentally ill parents is gaining attention. Moreover there is a lack of interventions for COPMI-children, as well of (cost-) effectiveness studies evaluating COPMI interventions. Innovative interventions such as e-health provide a new field for exploration. There is no knowledge about the opportunities for using the internet to prevent problems in children at risk. In the current study we will focus on the (cost-) effectiveness of an online health prevention program for COPMI-children. Methods/Design: We designed a randomized controlled trial to examine the (cost-) effectiveness of the Kopstoring intervention. Kopstoring is an online intervention for COPMI-children to strengthen their coping skills and prevent behavioral and psychological problems. We will compare the Kopstoring intervention with (waiting list) care as usual. This trial will be conducted entirely over the internet. An economic evaluation, from a societal perspective will be conducted, to examine the trial's cost-effectiveness. Power calculations show that 214 participants are needed, aged 16-25. Possible participants will be recruited via media announcements and banners on the internet. After screening and completing informed consent procedures, participants will be randomized. The main outcome is internalizing and externalizing symptoms as measured by the Youth Self Report. For the economic evaluation, healthcare costs and costs outside the healthcare sector will be measured at the same time as the clinical measures, at baseline, 3, 6 and 9 months. An extended measure for the intervention group will be provided at 12 months, to examine the long-term effects. In addition, a process evaluation will be conducted. Discussion: Recent developments, such as international conferences and policy discussions, show the pressing need to study the (cost-) effectiveness of interventions for vulnerable groups of children. This study will shed light on the (cost-) effectiveness of an online preventive intervention.