In this paper, optimality conditions and duality for E-differentiable semi-infinite programming with multiple interval-valued objective functions are investigated. We first establish KarushKuhn-Tucker necessary and sufficient optimality conditions for some types of efficient solutions of E-differentiable semi-infinite programming with multiple interval-valued objective functions. Then, we propose E-Wolfe and E-Mond-Weir type duality for the E-differentiable semi-infinite programming with multiple interval-valued objective functions, and explore weak and strong duality relations under generalized E-convexity.