A method of screening an HNF4 alpha agonist which involves: (1) the step of bringing a test compound into contact with cells expressing an HNF4 alpha gene and further expressing a reporter gene under the regulation of a gene promoter the expression of which is controlled by HNF4 alpha , in the presence of an acyl CoA synthase inhibitor; and (2) the step of measuring the expression dose of the reporter gene in the above cells. According to this method, the activation of HNF4 alpha originating in a substance contained in the screening system can be inhibited and thus an HNF4 alpha agonist can be screened more accurately with lowered background.