Colorectal cancer (CRC) is the second leading cause of cancer-related death. The prevalence of colorectal neoplasm is increasing. Many studies have shown that thyroid dysfunction may be connected with the higher risk of pancreatic and breast cancer, but only a few described the role of thyroid dysfunction and thyroid hormone (TH) replacement in the development and risk of CRC. The aim of this study is to summarise all findings and potentially elucidate the connection between TH imbalance and colorectal cancer. The systematic review was conducted according to PICO and PRISMA guidelines. We searched MEDLINE, ClinicalTrials.gov, www.clinicaltrialsregister.eu, and Cochrane Library databases using the following keywords: “((((thyroid OR hypothyroidism OR hyperthyroidism OR levothyroxine OR hashimoto OR graves OR thyroidectomy)) AND (colon OR colorectal OR CRC)) NOT hashimoto[Author]) NOT graves[Author])”. No filters were used. Of total of 3054 articles identified by the search strategy, 11 met PICO criteria and were included into the review. Four of those were on cell lines and seven were human studies. Analysis of the included studies revealed an elevated risk of CRC in patients with hypothyroidism with aORs ranging from 1.16 (95% CI: 1.08–1.24, p < 0.001) to 1.69 (95% CI: 1.21–2.36, p = 0.002). Moreover, TH replacement therapy has a protective effect for CRC risk with aOR ranging from 0.60 (95% CI: 0.44–0.81, p = 0.001) to 0.92 (95% CI: 0.86–0.98, p = 0.009). THs seem to play a role in colorectal carcinogenesis. Further studies are warranted to define the exact role of thyroid hormone imbalance in prevention and treatment of CRC. Colorectal cancer (CRC) is the second leading cause of cancer-related death. The prevalence of colorectal neoplasm is increasing. Many studies have shown that thyroid dysfunction may be connected with the higher risk of pancreatic and breast cancer, but only a few described the role of thyroid dysfunction and thyroid hormone (TH) replacement in the development and risk of CRC. The aim of this study is to summarise all findings and potentially elucidate the connection between TH imbalance and colorectal cancer. The systematic review was conducted according to PICO and PRISMA guidelines. We searched MEDLINE, ClinicalTrials.gov, www.clinicaltrialsregister.eu, and Cochrane Library databases using the following keywords: “((((thyroid OR hypothyroidism OR hyperthyroidism OR levothyroxine OR hashimoto OR graves OR thyroidectomy)) AND (colon OR colorectal OR CRC)) NOT hashimoto[Author]) NOT graves[Author])”. No filters were used. Of total of 3054 articles identified by the search strategy, 11 met PICO criteria and were included into the review. Four of those were on cell lines and seven were human studies. Analysis of the included studies revealed an elevated risk of CRC in patients with hypothyroidism with aORs ranging from 1.16 (95% CI: 1.08–1.24, p < 0.001) to 1.69 (95% CI: 1.21–2.36, p = 0.002). Moreover, TH replacement therapy has a protective effect for CRC risk with aOR ranging from 0.60 (95% CI: 0.44–0.81, p = 0.001) to 0.92 (95% CI: 0.86–0.98, p = 0.009). THs seem to play a role in colorectal carcinogenesis. Further studies are warranted to define the exact role of thyroid hormone imbalance in prevention and treatment of CRC.