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Colorectal cancer is one of the most aggressive types of cancer with about two million new cases and one million deaths in 2020. The side effects of the available chemotherapies and the possibility of developing resistance against treatment highlight the importance of developing new therapeutic options. The development in the field of nanotechnology have introduced the application of nanoparticles (NPs) as a promising approach in the diagnosis and treatments of colorectal cancer and other types of cancer. Gold nanoparticles (AuNPs) are currently one of the most studied materials as they possess unique tunable properties allowing them to play a role in colorectal cancer bioimaging, diagnosis, and therapy. The high surface-to-volume ratio of AuNPs mediates their utilization in drug delivery as well as functionalization to provide specific targeting. Moreover, depending on their physical properties (size, shape), AuNPs can be modified to fit the intended application. However, there are contradictory results around the pharmacokinetics of AuNPs including their biodistribution, clearance, and toxicity. This variation of opinions is most likely due to the development of different AuNPs that vary in shape, size, and surface chemistry, in addition to the conditions under which each research was carried out. The conflicting data represent a challenge in the clinical use of AuNPs suggesting the need to understand the toxicity, fate, and long-term exposure of AuNPs in vivo. Thus, there is an unmet need for the establishment of a publicly available data base for extensive analysis. In this review, we discuss the recent advances in AuNP applications in the treatment and diagnosis of colorectal cancer, mechanisms of action, and clinical challenges., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)