Background: Worldwide around 50 million people experience severe cognitive impairment. Limited study investigated whether the increased risk of cognitive impairment can be offset by a broad combination of healthy lifestyle behaviors in low- and middle-income countries. This study aims to perform a 10-year nationwide population-based prospective study for examining long-term association between combined multiple modifiable lifestyle factors and cognitive impairment. Method: We used four waves (2008-2018) of the Chinese Longitudinal Healthy Longevity Survey, including 8,321 participants aged ≥65 years with normal cognition at baseline. Exposures include dietary behaviors, single lifestyle behaviors (sleep, housework, exercise and social connection), and combined multiple behaviors. Cognitive impairment was assessed by the Mini Mental State Examination (score< 24). Cox proportional hazards models were performed to examine the long-term association between multiple lifestyle behaviors and cognitive impairment. Results: Of total 8,321 participants, 24.88% (2,070) developed cognitive impairment during a 10-year follow-up. This study showed a significant association of combined multiple behaviors with cognitive impairment [hazard ratio (HR) 0.55, 95%CI: 0.35 - 0.86]. Compared with participants who had unhealthy lifestyle activity and dietary behaviors, HR for cognitive impairment was 0.65 (95% CI: 0.45 - 0.94) and 0.91 (95% CI: 0.82 - 0.99) in those who had good lifestyle activity and dietary behaviors, respectively. Subgroup analyses revealed significant relationships in females and individuals with lowest education. Conclusions: Adherence to a broad range of healthy lifestyle factors was associated with a significantly lower risk of cognitive impairment. Behavioral lifestyle modification through multifactorial approaches should be a priority for prevention and delayed onset of cognitive impairment and dementia.