We studied the effect of matrine on rats with CRC using this network pharmacology approach, and we observed that matrine significantly suppressed CRC growth; this was associated with dysregulation of specific proteins (IL-6, TNF-α, HMGB1, and p53) and a corresponding pathway (HMGB1 signaling) and a function (Th cell differentiation). The gene discussed is HMGB1; the disease is colorectal carcinoma.