Background and Objective Activities of daily living (ADL) disability seriously affects the quality of life in the elderly. This study aims to examine the prevalence of ADL disability and its possible correlation with lipid profile indicators (LDL-C, TG and HDL-C) among female centenarians in Hainan, China. Methods A cross-section of complete sample study including 822 female centenarians was conducted from the China Hainan Centenarians Cohort Study (CHCCS) from June 2014 to December 2016. Barthel index was used to estimate ADL disability and multivariate logistic regression model was used to explore the relationship between lipid profile indicator and ADL disability. Results A total of 822 female centenarians were recruited in Hainan province, and the median age was 102 (IQR: 101–104) years, and 244 (29.7%) centenarians had ADL disability. After adjustment, 1 mmol/L increment in LDL-C, TG and HDL-C were associated with 26.4% (aOR=0.736, 95% CI:0.592–0.915), 29.8% (aOR=0.702, 95% CI:0.521–0.948) and 60.5% (aOR=0.395, 95% CI:0.257–0.610) decline in ADL disability of female centenarian, respectively. The prevalence of ADL disability showed downward trend with the increase of the quintile of LDL-C, TG and HDL-C (Ptrend<0.05). Increment of HDL-C levels had the strongest protective effect against ADL disability. Conclusion We concluded that a new possible association of higher normal lipid profile indicators, especially HDL-C, might have a protective effect on ADL disability among female centenarians.