Abstract  Long-term clinical observations and ongoing studies have shown antitumor effects of external Qi of Yan Xin Qigong (YXQG-EQ) that originated from traditional Chinese medicine (TCM). In order to understand the molecular mechanisms underlying the antitumor effects of YXQG-EQ, we investigate the effects of YXQG-EQ on growth and apoptosis in androgen-independent prostate cancer PC3 cells. We found that exposure to YXQG-EQ led to G2/M arrest associated with reduced cyclin B1 expression and apoptosis in PC3 cells. YXQG-EQ treatment inhibited constitutive and epidermal growth factor-induced Akt phosphorylation, basal and TNF-α-induced NF-κB activation, and downregulated anti-apoptotic Bcl-2 and Bcl-xL expression. In contrast, exposure to YXQG-EQ increased phosphorylation of Akt and Erk1/2 in human umbilical vein endothelial cells (HUVEC), and had no cytotoxic effect on either HUVEC or peripheral blood mononuclear cells (PBMC). These results indicate that YXQG-EQ has profound effects on growth and apoptosis of prostate cancer cells by targeting survival pathways including the Akt and NF-κB pathways.