Aim The present research study aimed to identify and compare the clinical and non‐clinical factors that predict the self‐reported and proxy‐reported health‐related quality of life (HRQoL) of people with major neurocognitive disorder (PwND) who are living at home in a Chinese society. Methods A total of 57 Chinese PwND‐family caregiver dyads that were using the services of local senior centers were recruited through a cross‐sectional survey with convenience sampling. Each PwND and caregiver rated the PwND's HRQoL independently by using the Quality of Life‐Alzheimer's disease measure. Additional measures included the Rosenberg Self‐Esteem Scale (RSES), Index for Managing Memory Loss, Geriatric Depression Scale, Cornell Scale for Depression in Dementia and Zarit Burden Inventory. Results The results of hierarchical multiple linear regression analyses showed that the PwND's self‐rated HRQoL and caregiver‐rated HRQoL were found to be predicted by different clinical and non‐clinical variables. In particular, the self‐esteem of PwND had the highest predictive power for the self‐rated HRQoL, whereas the caregiver burden is the only significant predictor for the caregiver‐rated HRQoL. Conclusions In the present study, the self‐esteem of PwND and the caregiver's burden were found to be important factors predicting self‐rated HRQoL and caregiver‐rated HRQoL respectively, which is probably because of the influence of traditional Chinese cultural values. Thus, it is important for non‐pharmacological interventions to address these special needs to promote HRQoL for this population. Geriatr Gerontol Int 2017; ••: ••–••.