Real-time fluorescence quantitative PCR（RT-qPCR） and Western blotting methods were used to detect the expression levels of GRP78 mRNA and protein in the liver cancer SMMC-7721， HepG2， PLC， Huh7 and QGY-7703 cells， then the high and low GRP78 expression liver cells were selected as the research objects. GRP78 was targeted silenced by RNA interference technique in highly expressed human liver cancer SMMC-7721 cells， which was named siGRP78-SMMC-7721（siGRP78 group）， and siNC-SMMC-7721 was used as control group（siNC group）. GRP78 was over-expressed in the low-expression liver cancer HepG2 cells by gene recombination technique， which was named Flag-GRP78-HepG2（Flag-GRP78 group），and empty vector 3×Flag-HepG2 was used as control group（3×Flag group）.After irradiation with 0， 2， 4， 6， 8 and 10 Gy X-ray， the survival rates of liver cancer cells in various groups were determined by MTT assay. The proliferation rates of liver cancer cells in various groups were determined by EdU fluorescence staining. Western blotting method was used to detect the expression levels of phospatidylinositol-3（PI3K）/protein kinase B（Akt） signaling pathway proteins.

The results of RT-qPCR and Western blotting methods showed that the expression levels of GRP78 mRNA and protein were the highest in SMMC-7721 cells and the lowest in HepG2 cells，so the SMMC-7721 and HepG2 cells were selected as the subjects.The MTT assay results showed that the survival rates of liver cancer cells were decreased with the increase of radiation dose；compared with siNC group， the survival rates of cells in siGRP78 group were significantly reduced after X-ray irradiation above 6 Gy（P<0.01）；compared with 3×Flag group， the survival rates of cells in Flag-GRP78 group were significantly increased after X-ray irradiation above 4 Gy （P<0.05 or P<0.01）.The EdU fluorescence staining results showed that compared with siNC group， the proliferation rate of cells in siGRP78 group was significantly decreased （P<0.05）；compared with 3×Flag group， the cell proliferation rate in Flag-GRP78 group was significantly increased （P<0.05）.The results of Western blotting method showed that compared with siNC group， the expression levels of phosphorylated PI3K（p-PI3K）and phosphorylated Akt（p-Akt） proteins in the cells in siGRP78 group were significantly decreased（P<0.01）. Compared with 3×Flag group， the expression levels of p-PI3k and p-Akt in the cells in Flag-GRP78 group were significantly increased（P<0.01）.

High expression GRP78 can decrease the radiosensitivity of liver cancer cells， and its mechanism may be related to the activation of PI3K/Akt signaling pathway.