To investigate the impact of lifestyle, apolipoprotein E (ApoE) gene, and their interaction on the risk for cognitive frailty in the elderly population in China. The study participants were from the Chinese Longitudinal Healthy Longevity Survey. The information about their lifestyles were collected by questionnaire survey, and a weighted lifestyle score was constructed based on coefficients associated with specific lifestyles to assess the combined lifestyle. ApoE genotypes were assessed by rs429358 and rs7412 single nucleotide polymorphisms. Cognitive frailty was assessed based on cognitive function and physical frailty. Cox proportional hazards regression model was used to analyze the association of lifestyle and ApoE gene with the risk for cognitive frailty and evaluate the multiplicative and additive interactions between lifestyle and ApoE gene. A total of 5 676 elderly persons, with median age [ (, )] of 76 (68, 85) years, were included, in whom 615 had cognitive frailty. The analysis by Cox proportional hazards regression model indicated that moderate and high levels of dietary diversity could reduce the risk for cognitive frailty by 18% [hazard ratio ()=0.82, 95%: 0.68-1.00] and 28% (=0.72, 95%: 0.57-0.91), respectively; moderate and high levels of physical activity could reduce the risk by 31% (=0.69, 95%: 0.56-0.85) and 23% (=0.77, 95%: 0.64-0.93), respectively. Healthy lifestyle was associated with a 40% reduced risk for cognitive frailty (=0.60, 95%: 0.46-0.78). ApoE ε4 allele was associated with a 26% increased risk for cognitive frailty (1.26, 95%: 1.02-1.56). No multiplicative or additive interactions were found between lifestyle and ApoE gene. Dietary diversity and regular physical activity have protective effects against cognitive frailty in elderly population. Healthy lifestyle can reduce the risk for cognitive frailty in elderly population regardless of ApoE ε4 allele carriage status.