Glucose regulated protein 78 (Grp78) is a chaperon which acts in the protein folding. Cell-surface Grp78 is present on the surface of different type cancer cells. There are evidences that acetylsalicylic acid (ASA) provides advantages when combined with other chemotherapeutic agents in cancer patients. Resistance is an important problem in cancer treatment and etoposide is a drug which develops resistance against itself. Our purpose in this study is to see how the ASA, either used alone or combined with etoposide, affect on the HepG2 cell viability and to investigate the relationship of this viability with the cell-surface Grp78. Thus 12 different groups were assigned. Control group, 0.5 μg/ml etoposide group, 2.5, 5, 10 mM ASA groups, 10 mM 2-deoxyglucose (2-DG) + 0.5 μg/ml etoposide group and the groups added to this group with 2.5, 5 and 10 mM ASA respectively, 10 mM 2-DG +2.5 mM ASA group, 10 mM 2-DG + 5 mM ASA group, 10 mM 2-DG + 10 mM ASA group. MTT test was applied for the follow up of the viability of the cells. When the viability in etoposite group was %84.5, the viability in 2-DG+etoposit group was %75.4. This shows that 2- DG decreases the viability of the cells a little. Also, when ASA is applied alone or combined with 2-DG, it caused decrease in the cell viability but this effect was more significant when combined with 2-DG. When etoposide and ASA were combined, the decrease in high-dose viability was more significant. Cell surface Grp78 levels were higher in the group in which 2-DG and ASA were combined each other than the group in which ASA was applied alone. All these results show that cell-surface Grp78 is important for ASA showing its effect. New treatment protocols focused on the cell-surface Grp78 in cancer treatment can be revealed by further studies.