Abstract: The psychobiology of stress involves two major components, the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS). Research has revealed the association between behavior problems and the psychobiology of stress, yet findings are inconsistent and few studies have addressed the moderate correlations between behavior problems. This study examines the individual and interactive effects of HPA and ANS on child behavior problems while taking into account the comorbidity of externalizing and internalizing problems. Four saliva samples were collected from each participant in a community sample (N = 429; aged 11-12 years; 50.49 % male), which were assayed for cortisol (HPA) and alpha-amylase, sAA (ANS). Children’s behavior problems were assessed using parent-report and self-report versions of the Child Behavior Checklist. Latent variables were constructed to represent trait-like individual differences in cortisol and sAA. Low levels of HPA axis activity were associated with higher levels of both externalizing and internalizing problems, but only among children with low ANS arousal. The association between externalizing and internalizing problems diminished to non-significant after taking into account the influence of HPA axis activity and ANS arousal, which suggests that the psychobiology of stress explains a fair proportion of comorbidity of behavior problems. The findings support that interaction between HPA axis and ANS functioning has potential to clarify prior mixed findings and advance our understanding of the child behavior problems.