Background: Behavior problems of children with autism spectrum disorder (ASD) bring many difficulties and stress to their parents, thus increasing their risk of depression. Recent studies have shown that the mindfulness and perceived social support may play significant roles in improving the depression of these parents as well as relieve their boundary of stress. However, related research conducted under the context of Mainland China is still limited, and no studies have yet explored the mediating effect of mindfulness and perceived social support on the relationship between behavior of children with ASD and depressive symptoms of parents in Mainland China. Objective: The present study aimed to examine the relationship between behavior problems of children with ASD and parents' depressive symptoms in Mainland China and focused on whether mindfulness and perceived social support may act as mediators in the association between child behavior problems and parents' depressive symptoms. Method: Participants were 286 Chinese parents of children with ASD. The Strengths and Difficulties Questionnaire (SDQ), the Center for Epidemiological Studies-Depression Scale (CES-D), the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), and the Interpersonal Support Evaluation List-12 (ISEL-12) were adopted to assess: child behavior problems, parental depressive symptoms, individual differences in mindfulness and perceived social support. Results: The direct effects of child behavior problems on parental depressive symptoms was statistically significant (direct effect = 0.137, SE = 0.043, p = 0.002). Child behavior problems also showed a significant indirect effect on parental depressive symptoms through mindfulness (indirect effect = 0.097, SE = 0.025, p < 0.001) and perceived social support (indirect effect = 0.088, SE = 0.023, p < 0.001). Conclusions: Two variables, mindfulness and perceived social support both played a mediating role in the influence of child behavior problems on parents' depressive symptoms. Parental depressive symptoms were significantly related to child behavior problems. Consistent with previous studies across diverse cultural backgrounds, the results of this study showed that the relationship between child behavior problems and parents' depressive symptoms was, in part, mediated by mindfulness and perceived social support of parents. Mindfulness interventions and effective social support for parents of children with ASD may be needed to help parents raise their children and relieve depressive symptoms.