In the present study, the antioxidant and anti-human liver cancer (HepG2) cells effects of bioactive peptides from cowhide collagen (BPCC) were evaluated. BPCC exhibited significant scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals ((60.09 ± 3.51)%), 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals ((77.40 ± 3.10)%) and hydroxyl radicals ((56.00 ± 2.30)%) as well as strong reducing power (0.320 ± 0.025). Meanwhile, BPCC effectively protected biomacromolecules including proteins, lipids and DNA from oxidative damage induced by Cu2+/H2O2 and 2,2’-azobis(2-methylpropionamidine) dihydrochloride (AAPH). Moreover, BPCC significantly inhibited cell viability of HepG2 cells in a dose-dependent manner with an estimated IC50 of 7.61 mg/mL. The results of 4’,6-diamidino-2-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) staining demonstrated the apoptotic morphological changes and cell mediated death in BPCC treated HepG2 cells. In addition, BPCC induced decrease of mitochondrial membrane potential (MMP) in HepG2 cells. Therefore, the present finding proved that BPCC encompasses significant antioxidant activity and anticancer property on HepG2 cells and can be used as alternative food antioxidants for cancer prevention benefits.