Objective To investigate the effect of different concentrations of salidroside on LDH, CK, AST and SOD release quantity in supernatant of human myocardial cells, and the changes of human myocardial cells activity, and To find the effect of salidroside on human myocardial cells and discuss the possible molecular mechanisms. Methods The hypoxic model in vitro was established and the LDH, CK, AST and SOD release quantity in supernatant of human myocardial cells dealt with different concentrations of salidroside were measured. Cell activity of different treatment groups was analyzed by CCK-8 assay. Apoptotic changes in HCM cells were observed by using Hoechst-PI staining. The expression of HIF-1α was determined by immunofluorescence. Results Compared with the hypoxia control group, the concentration of LDH, CK, and AST was significantly decreased and SOD was significantly increased with the dose-dependent dealt by different concentrations of salidroside (1×10-4, 10-5 and 10-6 mol/L). Salidroside significantly increased the activity of human myocardial cells with the dose-dependent. Compared with the hypoxia control group, human myocardial cell death and apoptotic of salidroside treatmentgroups (1×10-4, 10-5 and 10-6 mol/L) showed significant decreased trend. Hypoxia activated the HIF-1α expression. Conclusions Salidroside could significantly inhibit the release of LDH, CK and AST, and increase SOD content in human myocardial cells. At the same time, it can improve the activity and reduce apoptosis of human myocardial cells. The molecular mechanism may be related to HIF-1α expression.