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Objective To compare quality of life (QOL) and levels of anxiety and depression between primary caregivers of children with intellectual disabilities (ID) and caregivers of children without ID, and to identify sociodemographic and emotional correlates of caregivers’ QOL among those caring for children with ID. Methods A total of 217 primary caregivers of children diagnosed with ID were recruited from Jinzhou Kangning Hospital between January and December 2023, and 141 caregivers of children without ID from the same region were recruited online. Caregivers completed the WHOQOL-BREF, and trained psychiatrists administered the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD-17). Group differences were examined using t-tests and ANOVA, and Pearson correlations assessed bivariate associations. Within the ID caregiver group, hierarchical multiple regression (Enter method) was performed to evaluate the impact of sociodemographic covariates, anxiety, and depression on WHOQOL-BREF domains. Model improvement was assessed using ΔR² and F-change tests. Results Compared with the comparison group, caregivers of children with ID reported significantly lower QOL across all WHOQOL-BREF domains and significantly higher anxiety and depression. Within the ID caregiver group (N = 217), QOL was associated with caregiver kinship (relationship to the child), child characteristics, and family socioeconomic resources (e.g., income) in bivariate analyses. In multivariable models, adding anxiety and depression significantly increased explained variance in all domains in the ID caregiver group only (ΔR² = .034–.053). Anxiety independently predicted lower psychological well-being (PW) and social relationships (SR), whereas depression independently predicted lower environmental QOL (EN); neither symptom showed a unique association with physical capacity (PC) after adjustment. Several covariates remained significant in Model 1, including (selected examples) family income (PW, SR), profound ID (PW), caregiver kinship (SR), child gender (SR), and child age (EN). Conclusions In the context of family caregiving in China, caregivers of children with ID experience poorer QOL and greater emotional distress than caregivers of children without ID. Anxiety and depression contribute additional explanatory power beyond sociodemographic factors, with domain-specific patterns of independent association. These findings support the need for accessible psychosocial support and family-centered services, and for longitudinal research to clarify temporal pathways.