Background : Ephedra Sinica has been used to treat obesity in Korean medicine and brown adipocytes also have potential in obesity treatment. Recently, p53 is considered as one of transcriptional regulators regarding thermogenesis of brown adipocytes. Methods and Results : E. Sinica extraction was made with DW and brown preadipocytes were differentiated with adipogenic reagents by incubating for 6 days in the absence or presence of E. Sinica extraction 5 ㎍/㎖ and 10 ㎍/㎖, non-cytotoxic concentration determined by MTT assay. Studies were conducted to see whether E. Sinica modulates the expression of thermogenic and adipogenic genes by qPCR and Western blot. Results showed that E. Sinica significantly activated thermogenesis of brown adipocytes by increasing the mRNA expressions of Uncoupling Protein 1 (UCP1), Cell Death-inducing DNA Fragmentation Factor Alpha-like Effector A (CIDEA), Interferon Regulatory Factor 4 (IRF4) and Beta-3 Adrenergic Receptor (ADRB3). However, major adipogenic genes such as Peroxisome Proliferator-activated Receptor Gamma (PPARλ) and PR Domain Containing 16 (PRDM16), showed no significant differences. In addition, the expression level of p53 was decreased by E. Sinica. Conclusion : It is suggest that E. Sinica stimulates the thermogenesis of brown adipocytes via p53 inhibition.