To evaluate the in vivo immunomodulatory activity of the crude polysaccharide from Helicteres angustifolia L. (HACP), a 4T1 breast tumor model in BALB/c mice was used in this study. After tumor incubation for 6 days, mice were orally administered with 100, 200, and 300 mg/kg of HACP for 15 days. The results show that HACP administration resulted in a remarkable immunomodulatory effect attributable to the increased spleen and thymus indices, unregulated CD4⁺/CD8⁺ ratios in spleen lymphocytes, and the augmentation of IL-1β, IFN-γ, and TNF-α productions in the serum of tumor-bearing mice. The increased immunity resulted in a significant reduction in the tumor weight in 100, 200, and 300 mg/kg of HACP treatment groups, achieving inhibition rates of 34.58 ± 10.20%, 57.80 ± 8.65% and 67.71 ± 5.80%, respectively. In addition, a reduced lung metastasis was also detected in the HACP treatment groups. These findings, for the first time, provide scientific evidence that HACP can improve the immune response in 4T1 tumor-bearing mice, which plays a major role in the antitumor effect. Thus, HACP is prospectively valuable to be developed as new products with immunomodulatory activity and used for the treatment of breast cancer.