We present a flavor model of quarks and leptons with the non-Abelian discrete symmetry $S_4$ in the framework of the SU(5) SUSY GUT. Three generations of $bar 5$-plets in SU(5) are assigned to ${bf 3}$ of $S_4$ while the first and second generations of 10-plets in SU(5) are assigned to ${bf 2}$ of $S_4$, and the third generation of 10-plet is assigned to ${bf 1}$ of $S_4$. Right-handed neutrinos are also assigned to ${bf 2}$ for the first and second generations and ${bf 1}$ for the third generation. We predict the Cabibbo angle as well as the tri-bimaximal mixing of neutrino flavors. We also predict the non-vanishing $U_{e3}$ of the neutrino flavor mixing due to higher dimensional mass operators. Our predicted CKM mixing angles and the CP violation are consistent with experimental values. We also study SUSY breaking terms in the slepton sector. Our model leads to smaller values of flavor changing neutral currents than the present experimental bounds.