Epilepsy is not only a chronic neurological disorder but also a condition associated with other comorbidities. The purpose of this study was to determine the prevalence of major depression in a cohort of adult patients with epilepsy (PWEs) living in north China, and investigate the predictors of major depression in PWEs. A total of 215 consecutive cases were enrolled and divided into two groups: PWEs with major depression and PWEs without major depression. Patients were assessed for demographic characteristics, epilepsy details, and social status. A total of 65 of 215 (30.23%) PWEs exhibited comorbid major depression. A binary logistic regression model revealed the strong predictor variables of major depression to be drug responsiveness (odds ratio [OR]=0.23; p= 0<0.01; 95% CI [0.13-0.39]), presence of chronic medical illnesses (OR=0.19; p=0.015<0.05; 95% CI [0.05-0.72]), and employment status (OR=0.42; p=0.015<0.05; 95% CI [0.21-0.84]).