We propose an S_4 flavor model based on supersymmetric (SUSY) SU(5) GUT. The first and third generations of 10 dimensional representations in SU(5) are all assigned to be 1_1 of S_4. The second generation of 10 is to be 1_2 of S_4. Right-handed neutrinos of singlet 1 and three generations of 5̅ are all assigned to be 3_1 of S_4. The VEVs of two sets of flavon fields are allowed a moderate hierarchy, that is 〈Φ^ν〉∼λ_c〈Φ^e〉. Tri-Bimaximal (TBM) mixing can be produced at both leading order (LO)

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... next to next to leading order (NNLO) in neutrino sector. All the masses of up-type quarks are obtained at LO. We also get the bottom-tau unification m_τ=m_b and the popular Georgi-Jarlskog relation m_μ=3m_s as well as a new mass relation m_e=8/27m_d in which the novel Clebsch-Gordan (CG) factor arises from the adjoint field H_24. The GUT relation leads to a sizable mixing angle θ^e_12∼θ_c and the correct quark mixing matrix V_CKM can also be realised in the model. The resulting CKM-like mixing matrix of charged leptons modifies the vanishing θ^ν_13 in TBM mixing to a large θ^PMNS_13≃θ_c/√(2), in excellent agreement with experimental results. A Dirac CP violation phase ϕ_12≃±π/2 is required to make the deviation from θ^ν_12 small. We also present some phenomenological numerical results predicted by the model.