This study aims to investigate the inhibitory effect of Dendrobium Officinale Polysaccharide (DOPA) on growth of human breast cancer MCF-7 cells and the related mechanism. Human breast cancer MCF-7 cells were cultured and passaged. The cells were treated with DOPA with concentration of 5, 10, 20 and 40 mg/L. The cell activity was detected using MTT method, and the cell growth inhibition rate was calculated. The cell cycle and apoptosis were detected by flow cytometry. The protein expressions of LC3, p62, PI3K, Akt, p-PI3K, p-Akt and PTEN in cells were determined using Western blot assay. Results showed that, after treatment with DOPA, the growth of MCF-7 cells was obviously inhibited. When the treatment time was 48 h, the inhibition rate in 40 mg/L DOPA group was the highest, which was 35.43 ± 4.36%. The cell cycle was arrested in the G1 phase and S phase, and the total cell apoptosis rate in 40 mg/L DOPA group was 33.56 ± 4.02%. After treatment with DOPA, compared with control group, the protein expression levels of LC3-II and PTEN were significantly increased (P<0.05), and those of LC3-I, p62, PI3K, Akt, p-PI3K and p-Akt were significantly decreased (P<0.05). DOPA can inhibit the growth of human breast cancer MCF-7 cells. The mechanism may be related to its inhibition of PTEN/PI3K/Akt signaling pathway.