Hypothesis: Chaperone-mediated autophagy(CMA) selectively degrades intracellular proteins containing KFERQ motif. Many results have shown that AR7, the RARα antagonist, arouses CMA activation. However, we found that AR7 may decrease PPARα expression. PPARα plays a key role in lipid and glucose homeostasis. Recently, PPARα was proved to be the CMA activator. Therefore, several candidate chemicals were scanned to find the desired drug, which would down-regulate RARα expression and up-regulate PPARα expression at the same time. Result: Dual-luciferase reporter assay system was applied to detect the RARα and PPARα expressions. AR7 and WY-14643 were used as positive control respectively. Later, the mRNA and protein expression of LAMP2A and CMA substrates were measured to study on abilities for activating CMA. Afterwards, the protein level of LAMP2A in lysosomes was measured under the treatment of candidates at 10µM. Finally, the Nile red assay was taken to check the ability of candidates to lipid degradation. Conclusion: AR7 and WY-14643 can have combined function of CMA activation, which means that the combined RARα inhibition and PPARα activation function chemical can have better CMA activation than the single function chemical. Nowadays, CMA plays the important role in treatment of several diseases, especially NAFLD. The better CMA agonist could be possible to be the drug to improve NAFLD.