In a financial market model, we consider the variance-optimal semi-static hedging of a given contingent claim, a generalization of the classic variance-optimal hedging. To obtain a tractable formula for the expected squared hedging error and the optimal hedging strategy, we use a Fourier approach in a general multidimensional semimartingale factor model. As a special case, we recover existing results for variance-optimal hedging in affine stochastic volatility models. We apply the theory to set up a variance-optimal semi-static hedging strategy for a variance swap in both the Heston and the 3/2-model, the latter of which is a non-affine stochastic volatility model. * Corresponding author. Mail: Paolo.Di_Tella@tu-dresden.de. † MKR thanks Johannes Muhle-Karbe for early discussions on the idea of "Variance-Optimal Semi-Static Hedging". We acknowledge funding from the German Research Foundation (DFG) under grant ZUK 64 (all authors) and KE 1736/1-1 (MKR, MH) using the orthogonal component L in the GKW decomposition (2.3).Moreover, notice that, if L ∈ H 2 0 is orthogonal to L 2 (S) in the Hilbert space sense, then L is also orthogonal to S, i. e. LS is a martingale starting at zero and, in particular, L, S = 0. Therefore, from (2.3) we can compute the optimal strategy ϑ * by S, H = ϑ * · S, S = · 0