Abstract: In this essay, we discussed the philosophical basis of evidence-based medicine regarding epistemology.Medical practice mainly has been following rational reasoning for a long period of time. However, developments of modern epidemiology call rational reasoning in medicine into question. Evidence-based medicine endorses the central role of research evidence in decision-making. Therefore, its philosophical basis should be empiricism rather than rationalism. As empiricism does not completely exclude rationality from knowledge, evidence-based medicine does not use research evidence as a "one-size-fits-all" approach and claims that decisions can be based on rationality knowledge when lacking empirical observations. No matter what philosophical basis of evidence-based medicine is, the ultimate goal should always be achieving the largest benefits for patients in medical practice.