〔Abstract〕 Objective To construct the models of endoplasmic reticulum stress and autophagy through nutrient stress, and evaluate its effects on tumor proliferation and apoptosis. Methods HepG2 cells and Huh7 cells were treated with low-glucose DMEM containing 1% serum for different time. The endoplasmic reticulum stress marker proteins glucose regulatory protein 78(GRP78), activated transcription factor-6(ATF6), inositol requires 1α(IRE1α), include protein kinase RNA-like ER kinase(PERK)and autophagy-related proteins light chain 3(LC3),nucleoporin 62(P62), autophagy-related protein 1(Beclin-1) were detected by Western blot. Immunofluorescence was used to observe the co-localization of LC3 and GRP78. Flow cytometry was used to detect cell apoptosis rate. CCK-8 was used to detect cell proliferation. Results Western blot showed that nutrient stress increased the expressions levels of GRP78, ATF6, IRE1α, PERK, LC3, P62 and Beclin-1 in HepG2 cells and Huh7 cells in a time-dependent manner, and reached a peak at 36 h. Laser confocal microscopy further showed that the fluorescence intensity of GRP78 and LC3 significantly increased at 36 h. The flow cytometry showed that the low-glucose DMEM containing 1% serum did not increase the apoptosis of liver cancer cells. However, CCK-8 experiments found that nutrient stress could inhibit the proliferation of liver cancer cells. Conclusion Low-glucose DMEM containing 1% serum can not only induce endoplasmic reticulum stress and autophagy, but also not increase tumor cell apoptosis. The models are consistent with the real survival status of tumor cells, and provide a new and better method for studying endoplasmic reticulum stress and autophagy.