Background: Caregivers of children with disabilities might face high risk of anxiety, but the specific influencing factors may be different between parents and grandparents. Objective: This study is to explore the influencing modifiable factors from personal and environmental dimensions, so as to provide practical reference for effectively preventing and alleviating anxiety of this population. Methods: A total of 504 primary caregivers were investigated in Shanghai, China, of which 496 parents and grandparents were included in the analysis. Risk of anxiety was measured by the Generalized Anxiety Disorder 7-item (GAD-7) Scale. Descriptive statistics, univariate analysis, and multivariable logistic regression were performed to describe the personal and environmental characteristics of parents and grandparents, risk of anxiety, and identify the significant factors. Results: 35.1% of the total caregivers had the risk of anxiety, parents (35.8%) were slightly more anxious than grandparents (33.1%). Among parents, children's stable emotion (AOR=0.263, 95% CI=0.113, 0.611), higher household income (AOR=0.664; 95% CI=0.519, 0.850), owning a house (AOR=0.326; 95% CI=0.174, 0.610), and better barrier-free construction (AOR=0.400; 95% CI=0.170, 0.941) were associated with lower odds of anxiety. As for grandparents, significant association was merely found in caregiving time (AOR=2.936; 95% CI=1.064, 8.107). Limitations: Given the cross-sectional design, we would not infer causal relationships. Conclusions: Anxiety among family caregivers of children with disabilities was not encouraging and need to be urgently concerned. To reach optimal efficiency, intergenerational differences should be considered when health care providers and policy makers taking measures to facilitate the mental health of this population.