Antitumor activities of fullerene amino acids derivatives were systematically investigated in human cancer cell lines ----SGC-7901 and MCF-7 cell lines. Two fullerene amino acids derivatives have been prepared by chemical conjugation of L-phenylalanine (C60-phe) or glycine (C60-gly)to C60.The results showed that C60-gly or C60-phe inhibited the proliferation of human cancer cells, induced cancer cells apoptosis, and caused a significant perturbation of the cell cycle, with an accumulation of cells in the S phase and a substantial decrease of the cells in the G2-M phases. In addition, C60-phe or C60-gly was capable of inducing the rise of intracellular ROS after irradiated with a 25W incandescent lamp light source for 30min. Furthermore, C60-phe or C60-gly upregulated expressions of phosphorylated (p)p38MAPK, and NAC, an antioxidant and ROS scavenger, significantly depressed these C60 derivatives(C60-phe or C60-gly)-induced activation of p38MAPK, and prevented C60 derivatives-induced DNA damage. In addition, inhibition of p38MAPK with kinase inhibitor SB203580 significantly prevented C60 derivatives –induced cell apoptotic. These findings suggest that p38MAPK is activated by C60-phe or C60-gly through triggers ROS generation leading to cancer cell injuries.