Dysautonomia, a parasympathetic-sympathetic imbalance, has clinical and public health consequences. Colon neoplasm is linked to dysautonomia through a complex interplay between the two conditions. In this prospective cohort study, we evaluated 18 patients divided into three groups: six patients with both colon cancer and dysautonomia, six patients with colon cancer without dysautonomia, and six patients with dysautonomia only (control group). Dysautonomia was defined by the presence of orthostatic hypotension, a non-increased or dropped heart rate, and various autonomic symptoms. During abdominal surgery, tissue samples from the celiac ganglion were collected and analyzed using immunohistochemistry (IHC). Our findings revealed a significant correlation between IHC marker expression in colon cancer and dysautonomia (control) (r = 0.927, P = 0.008). ANOVA results confirmed that the model was significant and that the dysautonomia group (control) had a significant effect on the independent variables (colon cancer or colon cancer + dysautonomia). The study proposes that a shared immunological mechanism underlies both dysautonomia and colon cancer, suggesting that the immune system plays a crucial role in the development or progression of these two conditions.