Objective: Cancer is associated with some psychological problems that play an important role in the severity and continuity of cancer. Cancer may lead to maladaptive psychological reactions such as anxiety, depression, and fatigue. Depression and anxiety are highly prevalent in cancer patients. This study aimed to compare the efficacy of mindfulness-based cognitive therapy (MBCT) and cognitive behavioral therapy (CBT) for anxiety, depression, and fatigue in cancer patients. Method: The present study was a randomized clinical trial (RCT). Of the 100 patients diagnosed with cancer, 60 patients were eligible to participate in this study according to the inclusion / exclusion criteria. They were randomly assigned into 3 groups: MBCT, CBT, and wait-list group (WLG). Afterward, the experimental groups received 8 weekly treatment sessions. All the participants fulfilled the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Cancer-Related Fatigue Scale (CFS) before and after the intervention. Data were analyzed using SPSS-16 software by Analysis of Covariance (ANCOVA). Results: The results indicated a significant reduction in depression, anxiety, and fatigue scores in CBT and MBCT groups. There was a significant difference between both treatment groups with WLG in the anxiety and depression, but no significant difference was found between MBCT and CBT groups. Additionally, there was only a significant difference between the CBT group and WLG in terms of fatigue (P = 0.01). Conclusion: CBT and MBCT performed equally well in decreasing anxiety and depression in cancer patients, and they were significantly better than WLG. It seems that MBCT is a good alternative to CBT for decreasing emotional symptoms in cancer patients. As a result, CBT and MBCT could be considered a good addition to pharmacological treatment of cancer patients with comorbid psychological symptoms. However, CBT was preferable to MBCT in decreasing fatigue. The study was registered at the irct.ir database under registration number IRCT20180503039509N1.