•Depression is a common comorbid mental disorder in people with epilepsy.•In Vietnam, the prevalence of major depression in a hospital-based sample is 25.3%.•The Vietnamese version PHQ-9 is a useful and valid screening tool for depression in epilepsy in busy clinic settings. Depression is a common mental disorder in people with epilepsy. Depression has a negative impact on medical and surgical treatment of epilepsy thus affecting the quality of life. Despite its high prevalence, depression has been under-recognized and treated improperly. It may also lead to missed work, increased healthcare system utilization, and higher direct medical costs. This study aimed to evaluate the accuracy of the Vietnamese Patient Health Questionnaire (PHQ-9) as a screening tool for depression in people with epilepsy. This cross-sectional study was conducted prospectively at epilepsy clinic at Nguyen Tri Phuong hospital, Ho Chi Minh City, Viet Nam from December 2019 to March 2020. A total of 91 adult people with epilepsy were recruited. After completing the Vietnamese PHQ-9 questionnaires, each participant was interviewed in a structured clinical interview for DSM-5 (SCID-5) to establish a diagnosis of major depressive disorder. The diagnostic accuracy of the PHQ-9 was assessed using diagnostic efficiency statistics compared with the gold standard structured interview. The prevalence of major depression in this sample was 25.3%. The areas under receiver operating characteristic (ROC) curve index of PHQ-9 had an estimated value of 0.91. The PHQ-9 at a cutoff point of 8 had the great overall balance of sensitivity (87.0%) and specificity (82.4%). At the cutoff point of 10, PHQ-9 had a higher specificity of 94.1%, but a lower sensitivity of 78.0%. The Vietnamese version PHQ-9 is an efficient and valid screening tool for depression in people with epilepsy in clinic settings.