Background ApoE gene polymorphism and serum total homocysteine (tHcy) has been reportedly associated with cognition. In this study, we assessed the association of combined ApoE gene polymorphism and tHcy with cognition in Chinese elder adults. Methods A cross- sectional study was carried out by recruiting 1458 community-dwelling people aged 55+ and above in Beijing in 2009. All participants were interviewed using a standard questionnaire and underwent a physical examination. The mini-mental scale examination (MMSE) score was used in assessing cognitive function. Fasting venous blood samples were taken for ApoE rs429358, rs7412 genotyping, tHcy and other serum lipid measurements. Results Participants with high serum tHcy level showed a relatively lower orientation, attention abilities as well as the total MMSE score than the group with normal tHcy after adjusting confounding factors. ApoE rs429358 and rs7412 variants were observed to have the highest serum TC and TG level in the subjects with high serum tHcy level (p < 0.05). Cognition of the subjects was found to be significantly associated with high serum tHcy level and ApoE genetic polymorphism (p < 0.05). Independent of age, BMI, education levels, smoking and alcohol drinking, the worst cognitive ability were detected in the high serum tHcy level subjects with ApoE rs429358C/T and rs7412 C/T as compare with other groups, especially orientation function, memory and delayed recall ability and attention ability. Conclusion High serum tHcy level in combination with ApoE rs429358 and rs7412 variants might be linked with serum lipid levels and cognition, particularly for orientation function and memory and delayed recall ability in old Chinese adults.