C-Phycocyanin (C-PC) from blue-green algae has been reported to have various pharmacological characteristics, including anti-inflammatory and anti-cancer activities. In this study, the beta-subunit of C-PC (ref to as C-PC/beta) was expressed and purified from bacteria E. coli BL-21. The recombinant C-PC/beta has been demonstrated to have anticancer properties. Under the treatment of 5 microM of the recombinant C-PC/beta, four different cancer cell lines accrued a high proliferation inhibition and apoptotic induction. The C-PC/beta interacts with membrane-associated beta-tubulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been found. Under the treatment of the C-PC/beta, depolymerization of microtubulin and actin-filament was observed. The cells underwent apoptosis with increase of Caspase-3 and Caspase-8 activities. Cell cycle was arrested at G0/G1 phase under the treatment of C-PC/beta. In addition, the nuclear level of GAPDH decreased significantly. Inhibition of cancer cell proliferation and induction of apoptosis may potentate C-PC/beta as a promising cancer prevention or therapy agent.