We use open-closed string duality between F-theory on K3xK3 and type II
strings on CY manifolds without branes to study non-perturbative
superpotentials in generalized flux compactifications. On the F-theory side we
obtain the full flux potential including D3-instanton contributions and show
that it leads to an explicit and simple realization of the three ingredients of
the KKLT model for stringy dS vacua. The D3-instanton contribution is highly
non-trivial, can be systematically computed including the determinant factors
and demonstrates that a particular flux lifts very effectively zero modes on
the instanton. On the closed string side, we propose a generalization of the
Gukov-Vafa-Witten superpotential for type II strings on generalized CY
manifolds, depending on all moduli multiplets.