Background: Cancer is a fatal disease in Saudi Arabia. According to WHO, “Cancers are the leading causes of mortality, with approximately 14 million new cases and 8.2 million cancer-related mortalities in 2012.” Additionally, about 25% of cancer patients experience depression. This study aims to estimate the prevalence of depression among cancer patients. Our study is a cross-sectional study and was conducted at Princess Noorah Oncology Center in King Abdulaziz Medical City, Jeddah. Subjects and Methods: We studied patients (≥ 18 years old) in both genders with confirmed cancer diagnosis regardless of treatment initiation and who were aware of their diagnosis. The study consisted of 281 patients. Results: Most patients were female (55.5%). For patients by age groups, 112 patients (39.9%) were at age group of 40 to 59, 91 patients (32.4%) were at ≥ 60 years old, 62 patients (22.1%) aged 20 to 39 and 16 patients (5.7%) aged < 20 years old. The most important factor causing depression among cancer patients was the number of chemotherapy cycles (p-value = 0.012). Additionally, based on the analysis of Patient Health Questionnaire-9 (PHQ9) scores, only 95 patients (33.8%) had no depression, while the rest suffered from varying degrees of depression. Mild depression 112 patients (39.9%)] was the most common among patients with depression. Conclusion: Early detection of depression is essential to enhance compliance and prognosis. However, further research is necessary to develop a standardized approach to mitigate depression among cancer patients. Key words: Saudi Arabia, Depression, Cancer, PHQ9.