Objective To explore the role of serum cortisol level in differentiating Alzheimer disease （AD） from senile depression. Methods The serum cortisol level， estradiol， growth hormone and other hormone levels of patients aged from 55 to 95 who were diagnosed as depressive disorder or AD according to ICD-10 diagnostic criteria and discharged from the Department of Geriatric Psychiatry， Suzhou Guangji Hospital from January 1， 2018 to October 1， 2020 were analyzed retrospectively. Results A total of 109 patients with depression and 57 patients with AD were included in the study. The cortisol level in depression group was significantly higher than that in AD group ［478.10（389.81， 587.63） nmol/L vs 370.30 （290.66， 405.35） nmol/L； Z=5.91， P＜ 0.01］， while the age ［（69.68±8.01） vs （75.77±8.01）； t=4.66， P＜ 0.01］， luteinizing hormone ［18.90 （9.59， 27.60） IU/L vs 24.31 （15.18， 34.06） IU/L； Z=2.27， P=0.02］and growth hormone ［0.23 （0.10， 0.73） ng/ml vs 0.30 （0.20， 1.45） ng/ml； Z=2.02， P=0.04］were significantly lower than those in AD group. Two indexes， age （OR=0.92， 95%CI： 0.88-0.96， P＜0.01） and cortisol （OR=1.01， 95%CI： 1.00-1.01， P＜0.01）， were selected by logistic regression to construct regression equation. The area under ROC curve of age， cortisol and the combination of age and cortisol were 0.69 （95%CI： 0.62-0.76）， 0.78 （95%CI： 0.71-0.84） and 0.82 （95%CI： 0.75-0.88）， respectively. Conclusions Serum cortisol level may be used as an important index to differentiate senile depression from AD in hospital.