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The use of blood liquid biopsy is increasingly being incorporated into the clinical setting of gastrointestinal cancers care. Clonal hematopoiesis (CH) occurs naturally as a result of the accumulation of somatic mutations and the clonal proliferation of hematopoietic stem cells with normal aging. The identification of CH-mutations has been described as a source of biological noise in blood liquid biopsy. Incorrect interpretation of CH events as cancer related can have a direct impact on cancer diagnosis and treatment. This review summarizes the current understanding of CH as a form of biological noise in blood liquid biopsy and the reported clinical significance of CH in patients with GI cancers.