Reversing effects of traditional Chinese medicines on colorectal tumor immunosuppressions of natural killer (NK) cell and T lymphocyte were analyzed to provide evidence on selecting medicines for patients according to the different types of tumor immunosuppression. Six traditional Chinese medicines, including Arsenious acid (AS), Ligustrazine hydrochloride (LHC), Astragalus mongholicus bge (AMB), Matrine N-oxide (MOX), Polyporus umbellatus polysaccharide (PUPS) and Artesunate (ART), were enrolled. The reversing effects on suppression of murine splenocyte transformation and NK killing activity were measured by 3-{4,5-dimethyl-2-thiazolyl}-2,5-diphenyl tetrazolium (MTT), and the effects on the suppressed expression of interleukin 2 receptor α (IL-2Rα), CD3ɛ+ξ+ and CD3ɛ−ξ+ were detected by flow cytometry (FCM). The effects on immunosuppressive molecules were measured by enzyme linked immunosorbent assay (ELISA), including transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF), interleukin 4 (IL-4), IL-6, IL-10 and prostaglandin (PG) E2. (1) The reversing effects of AMB on the inhibition of NK killing and CD3ɛ+ξ+ expression were the most significant; the effect of LHC on inhibition of CD3ɛ−ξ+ expression was the strongest; the effects of AMB, PUPS and ART on inhibition of transformation were the greatest; and the effect of ART on inhibition of IL-2Rα expression was the strongest. (2) The correlated molecules of these medicines that exerted reversing effects on colorectal tumor immunosuppression were TGF-β1 and IL-10. AMB had the highest down-regulating effect on the secretion of TGF-β1. AS and ART had the highest effects on IL-10. Reversing tumor immunosuppression through the down-regulation of immunosuppressive molecules is one of the novel antitumor mechanisms of traditional Chinese medicines. The clinical use of compounded prescriptions of ART combined with AMB and LHC should be considered to avoid the reduced treatment efficiency caused by tumor immunosuppression.