Background: A cancer's diagnosis can have a substantial impact on mental health and wellbeing. Depression may hinder cancer treatment and recovery. Cognitive behavioral therapy is one of the most evidence-based psychological interventions for the treatment of several psychiatric disorders such as depression. Aim: This study aims to explore the effect of cognitive behavioral nursing intervention program on depression among cancer patients. Subjects and Method: Design:  A quazi- experimental design (pre, post, and follow-up evaluation) was used. Setting: Oncology unit at Al Shifa Medical Complex in Port Said city. Subjects: The study subjects included 63 patients with cancer. Tools: Two tools were utilized to collect the data, Beck Depression Inventory and Dealing with Illness Inventory; in addition to personal and clinical data sheet. Results: The study revealed less than half (41.7%) studied patients with cancer had mild level of depression at pre intervention, while more than one quadrant (26.7) had mild level of depression at post intervention. Also, less than half (45%) of the studied patients with cancer had moderate level of depression at pre intervention, while more than one third (36.6%) of them had moderate level of depression at post intervention.  Conclusion The cognitive behavioral nursing intervention program had significant lower level of depression among the studied cancer patients at post program compared to preprogram (P=0.000**). Recommendations: Therefore, cognitive behavioral interventions should be utilized in combination with standard care for cancer patients