Abstract: Objective: Effects of phycobiliprotein and phycocyanin from artifically raised Nostoc sphaeroides Kützing on the growth of tumor in S180 tumor-bearing mice and its mechanism. Methods: The in vivo antitumor activity of phycobiliprotein and phycocyanin from Nostoc sphaeroides Kützing was evaluated by examining the tumor volume of S180 tumor-bearing mice, mouse organ indices and tumor tissue section observation, and its mechanism of action was initially studied. Results: The results of in vivo antitumor effect showed that the tumor inhibition rates of phycobiliprotein 12.5, 25 and 50 mg/kg dose groups were 11.19%, 20.14% and 37.65%, respectively, against mouse sarcoma S180. The tumor inhibition rates of phycocyanin 12.5, 25 and 50 mg/kg dose groups were 19.74%, 35.00% and 52.06%, respectively, against mouse sarcoma S180. Phycocyanin significantly promoted the expression of oncoprotein P53 and pro-apoptotic protein Bax, and inhibited the expression of apoptosis suppressor protein Bcl2. Conclusion: Phycocyanin high dose group significantly reduced the proliferation of S180 sarcoma cells. Phycocyanin low and medium doses and phycocyanin high doses also had some inhibitory effects. Phycobiliprotein and phycocyanin from artifically raised Nostoc sphaeroides Kützing have better in vivo antitumor activity.