BACKGROUND: Depression is strongly associated with colorectal cancer (CRC). Few bibliometric analyses have systematically summarized the research focus and recent progress in this field. AIM: To determine the research status and hotspots by bibliometric analysis of relevant publications on the relationship between CRC and depression. METHODS: Articles on depression in CRC patients were collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were used to visualize bibliometric networks. RESULTS: From 2001 to 2022, , the United States, Tilburg University, and Mols were the most productive and influential journal, country, institution, and author name. Co-occurrence cluster analysis of keywords placed quality of life, anxiety, and psychological stress in the center of the visual network diagram. Further clustering was performed for the clusters with studies of the relevant mechanism of action, which showed that: (1) Cytokines have a role essential for the occurrence and development of depressive disorders in CRC; (2) MicroRNAs have a role essential for the development of depressive disorders in CRC; (3) Some anticancer drugs have pro-depressant activity; and (4) Selective serotonin reuptake inhibitors have both antitumor and antidepressant activity. CONCLUSION: Life quality and psychological nursing of the cancer population were key topics. The roles of cytokines and microRNAs, the pro-depression activity of anticancer drugs and their antitumor properties deserve in-depth study.