Purpose: This study aimed to investigate the contributing factors to health related quality of life (HRQoL) and depression levels of mothers in families having children with chronic disabilities. Methods: The study was designed as a cross-sectional survey including 580 families recruited from 45 cities across Turkey. HRQoL, depression levels and impact of chronic disabilities of a child on the mothers were gathered by using Nottingham Health Profile, Beck Depression Inventory and Impact on Family Scale (IPFAM), respectively. Other data were acquired using a face-to-face interview method. Findings: Regression analysis showed that the time spent for daily caring activities, disruption of social relations and coping subscale-scores of IPFAM were significant contributors to poor HRQoL and higher depression levels (p<0.05). Conclusion: The results suggest that providing a release time from daily caring tasks, increasing level of social interaction and provision of sustained assistance to help to develop coping strategies, would likely increase HRQoL and decrease level of depression of the mothers.