Cordyceps sinensis mycelium polysaccharide has been reported to regulate immune function, but its anti-lung cancer efficacy and its role in regulating the polarization of TAMs remain unelucidated. This study aims to investigate the anti-lung cancer activity of Cordyceps sinensis mycelium polysaccharide CP1 and its related mechanism. In vivo studies confirmed CP1 (40,80 or 160 mg/kg, i.p.) inhibited the A549 tumor growth, reduced the proportion of M2 macrophages infiltration in tumor tissues and the levels of IL-10 and TGF-β in serum of mice. In vitro, CP1 (80 μg/mL) lowered the mRNA levels of CD206, IL-10, Arg-1 and TGF-β, all markers indicative of M2 macrophage polarization. And CP1 decreased the proportion of M2 macrophages and reduced the secretion of IL-10 and TGF-β. Intriguingly, CP1 did not exhibit a direct inhibitory effect on A549 lung cancer cells. However, it did inhibit the proliferation, migration, and invasive abilities of these cells, achieved by modulating the M2 polarization of TAMs. This research revealed that CP1 may exert anti-lung cancer effects in vitro and in vivo by inhibiting M2 polarization of TAMs.