The main challenge of present paper is analytical comparing the “Criterion of Valid Cognition” from viewpoints of Epicureanism and Charvaka (Lokayata) philosophy, the largest exponent of Indian materialism,. The new findings of the research show that the whole construction of ontology, ethics, and infidelity of Charvaka is logically based on its epistemology. In this philosophy, any intangible existence is denied, and the only knowledgeable subject-matter is assumed to be the material world. So here firstly, the acquisition of the truth is possible solely by sensory instruments, and secondly, every ‘should’ and ‘should not’ that it is in contrary to the principle of material pleasure is negated. It can be said that the Charvaka’s philosophers consider Cognition as the ‘true and perceptible belief, but not reasonable one’, and they intensely questioned the validity of Inference, Testimony and Analogy. In contrast, the Epicurean philosophers seem to agree with the definition of Cognition as the ‘true and justifiable conviction’. In spite of believing in the originality of matter and regarding the ‘clarity of sensory perception’ as the criterion of truth, Epicureans consider also Inference, General Concepts and Emotions as the resources of cognition. Epicureanism’s epistemology is entirely rational, but that of Charvaka is irrational, empirical, contradictory, sense-based and contrary to Reality.