Abstract: Objective To explore the effects of Carfilzomib （CFZ） combined with irinotecan （CPT-11） on the proliferation， apoptosis and NF-kappa B of gastric cancer SGC-7901 cells. Methods The proliferation inhibition rates after treatment with different concentrations of CFZ （0， 0.1， 1， 10， 50，100nmol／L）， CPT-11 （0， 2.5， 5， 10， 50， 100μmol／L） or 100nmol／L CFZ plus 100μmol／L CPT-11 were analyzed via MTT colorimetric assay at 24， 48， 72 and 96h. The flow cytometry with Annexin V／PI double staining was used to evaluate the combined effect of CPT-11 and CFZ on apoptosis and cell cycle at 48h， respectively. The intracellular activation of caspase-3 was detected by flow cytometry. Western blotting method was used to measure the protein levels of NF-κB and IκB-α as well as the activation status of PI3K／Akt signaling pathway. Results The co-administration of CFZ and CPT-11 or single-agent treatment could increase the proliferation inhibition rates of SGC7901 cell in a time- and dose-dependent manner， while there were higher proliferation inhibition rate in co-administration versus singleagent treatment （P＜0.05）. Compared with the single-agent treatment， the co-administration of CFZ and CPT-11 presented increasing apoptosis rate， activation rate of caspase-3， proportion of S phase and IκB-α level but decreasing proportion of G2／M cell phase， NF-κB p65 and p-Akt level （P＜0.05）. Conclusion Both CFZ and CPT-11 exhibited cytotoxicity on SGC-7901 cell， including proliferative inhibition， induction of apoptosis， downregulation of NF-kappa B and suppression of the activation of PI3K／Akt signaling pathway. CFZ combined with CPT-11 have a synergistic effect on gastric cancer cells.