Bee pollen extract (BPE)-based polymer nanoparticles (BPENP) were fabricated by using bovine serum albumin (BSA) and targeted with folic acid and were further characterized. Mice groups are : Group 1 received saline, whereas Groups 2, 3, 4, 5, and 6 received a single dose of urethane, followed by weekly injections of butylated hydroxy-toluene (BHT). After the BHT injection, the mice in Groups 3, 4, 5, and 6 received BPE, Avastin,BPENP, and BNENP + Avastin, respectively. The number and size of tumors decreased in Group 6 compared to those in the other groups. The ratios of early and late apoptotic cells in Groups 3, 4, 5, and 6 (42.8%, 41.4%, 26.2%, and 45.4%, respectively) were lower than that in the untreated group. The PCNA-labeling indices (LI)% in tissues and lesions from Group 6 were lower than those in the other groups; on the other hand, the caspase 3 LI (%) was higher than those in the other groups. No significant differences in HRAS and MAPK levels were observed between Group 6 and the other groups. However, the level of Baxwas significantly increased, whereas those of Bcl2 and P21 were decreased in Group 6 compared to those in Groups 4 and 5.