Objective: To investigate the burden of caregivers of elderly patients with chronic diseases and its influencing factors, so as to provide the evidence for reducing the burden of caregivers. Methods: The caregivers of patients with chronic diseases at ages of 65 years and older were selected using convenience sampling method from Jinqiu Hospital during 2020 and 2021. The burden of caregivers was estimated using Chinese version of Caregiver Burden Scale (CBI), the basic information of patients and caregivers was collected, and the influencing factors of caregivers' burden were identified using multivariable linear regression analysis. Results: Totally 276 questionnaires were distributed, and 261 were valid, with an effective rate of 94.57%. There were 48 men (18.39%) and 213 women (81.16%), 166 (63.60%) subjects aged 45 to 59 years and 354 (82.38%) subjects participating in training on COVID-19 prevention. The mean score of caregivers' burden was 26.27±14.93, and the mean scores of social burden and emotional burden were 11.08±5.23 and 7.81±6.24, respectively. The patients with chronic diseases included 183 men (70.11%), had a mean age of (89.97±8.26) years, had a mean score of activities of daily living of 20.00 (interquartile range, 50.00) and had a mean geriatric syndrome number of 4.10±1.57. Multivariable linear regression analysis identified caregivers' participating in training on COVID-19 prevention (β'=0.175), patients' activities of daily living (β'=-0.144), patients' geriatric syndrome number (β'=0.138) and patients' age (β'=0.162) as factors affecting the burden of caregivers. Conclusions The social and mental burden of the caregivers of elderly patients with chronic diseases is heavy, and patients' activities of daily living, number of geriatric syndromes and age, as well as caregivers' training on COVID-19 prevention may be associated.