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Background: Anticipatory grief has been shown to be highly prevalent among family caregivers of patients with advanced illness. Qualitative study suggests that illness uncertainty may be one of the core characteristics of anticipatory grief, but it has not been confirmed in quantitative studies. Therefore, the purpose of this study was to explore the relationship between anticipatory grief and illness uncertainty among Chinese family caregivers of patients with advanced lung cancer and to determine the factors influencing anticipatory grief. Methods: This descriptive cross-sectional study used a convenience sampling method and recruited 254 inpatient family caregivers from the thoracic medicine ward of Liaoning Cancer Hospital & Institute in Shenyang, mainland China. Anticipatory grief (Anticipatory Grief Scale (AGS), illness uncertainty (Uncertainty in Illness Scale Family Caregiver Version) and sociodemographic information (Self-compiled general information questionnaire) were measured using validated self-report measures. Results: Chinese family caregivers of patients with advanced lung cancer had high levels of anticipatory grief (73.5 ± 16.1). The results of the correlation analysis showed a positive association between anticipatory grief and illness uncertainty (r = 0.580, P < 0.001). The final linear regression model with anticipatory grief as the dependent variable included four variables: illness uncertainty (β = 0.674, P < 0.001), lack of informativeness (β = − 0.168, P = 0.08), monthly income (β = 0.139, P = 0.006), and caregiving burden (β = − 0.196, P < 0.001). Conclusions: Illness uncertainty is probably an important factor affecting anticipatory grief. Excessive caregiving burden is associated with high levels of anticipatory grief. Improving illness uncertainty and caregiving burden may effectively reduce anticipatory grief among Chinese family caregivers. [ABSTRACT FROM AUTHOR]