In the present study, we investigated whether polymorphism of ARNTL2 (BMAL2) gene rs2306074 T/C was associated with susceptibility of Alzheimer disease (AD) in Chinese population. A case-control method was employed in this study. 296 unrelated AD patients and 423 control subjects were recruited in current study. The prevalence of C carriers in BMAL2 gene rs2306074 T/C in AD patients was significantly higher than that of control subjects in both the whole sample and APOE ε 4 non-carriers (in the whole sample: χ (2) = 5.938, P = 0.012; in APOE ε 4 non-carriers: χ (2) = 9.048, P < 0.0001). In addition, both in the whole sample and APOE ε 4 non-carriers, prevalence of CC genotypes in BMAL2 gene rs2306074 of AD patients was also significantly higher than that in controls (in the whole sample: χ (2) = 5.126, P = 0.018; in APOE ε 4 non-carriers: χ (2) = 7.389, P = 0.023). However, there was no significant difference of prevalence of C carriers and CC genotypes in BMAL2 gene rs2306074 T/C between AD patients and control subjects among APOE ε 4 carriers (C carriers: χ (2) = 0.020, P = 0.900; CC genotypes: χ (2) = 0.017, P = 0.946). C carriers in BMAL2 gene rs2306074 T/C are associated with a high susceptibility of AD among APOE ε 4 non-carriers but not among APOE ε 4 carriers in Chinese population.