INTRODUCTION: Depression is a condition that often arises in patients with cancer. As in many cases, the simultaneous use of anticancer drugs (ACD) and antidepressants (AD) may result in potential drug interactions that can lead to worsened medical outcomes and poorer quality of life in these patients. It is therefore essential that such interactions are carefully considered when treating patients for depression who already have cancer. AREAS COVERED: The objective of this article is to discuss the potential anticancer-antidepressant drug (ACD-AD) interactions that may be clinically important in cancer patients. This systematic review describes the drug-drug interactions (DDIs) encountered for each tumour type so that oncology practitioners can target specific sections of the paper based on their specific clinical interests and specialties. EXPERT OPINION: From our knowledge, there is currently no oncology-specific database that allows for DDI searches by both individual ACDs and multiple-agent chemotherapy regimens. Therefore, one-stop consolidated databases like OncoRx have been developed to reduce the time and effort for conducting DDI searches. The authors believe that epigenetic therapy combined with the rapid development of the semantic web can improve the scientific knowledge and lead to the development of new databases in the near future with novel strategies of detecting DDIs, so that the pharmaceutical care of cancer patients will ultimately be improved.