Objective To investigate the protective effect of 3-hydroxybutyrate derivate( methyl-3-hydroxybutyrate and ethyl-3-hydroxybutyrate)on the apoptosis of PC12 induced by FBS deficiency. Methods Methyl-3-hydroxybutyrate and ethyl-3-hydroxybutyrate were prepared by chemical degradation. PC12 cells were divided into different groups:medium with FBS as negative control,medium without FBS as positive control,medium with different concentrations of methyl-3-hydroxybutyrate or ethyl-3-hydroxybutyrate without FBS as sample groups. The shape and viability of cells in each group were analyzed by optical microscope and MTT. Results Compared with the negative control,cells in the positive control group demonstrated a large number of apoptosis,smaller and thinner morphology,and lower activity. However,the activity of cells was improved in the sample groups.Low concentration(0. 01 and 0. 001 mg·mL-1)of methyl-3-hydroxybutyrate and ethyl-3-hydroxybutyrate showed a protective effect on cell apoptosis,and 1 mg · mL-1 had the best protection effect. Conclusion High purity methyl-3-hydroxybutyrate and ethyl-3-hydroxybutyrate can be produced by chemical method,and both chemicals present good effect on protecting the PC12 from apoptosis.