We compute in the instanton vacuum the nucleon matrix elements of the twist-4 QCD operators describing power corrections to the second moments of the unpolarized structure functions, F L and F 2 . Our approach takes into account the leading contribution in the packing fraction of the instanton medium, /R 1 . Parametrically leading are the matrix elements of a twist-4 quark-gluon operator, which are of the order of the inverse instanton size, 1/ 2 =(600MeV) 2 . The matrix elements of the four-fermion (diquark) operators are suppressed by a factor (/R) 4 and numerically small. These results are in agreement with the pattern of phenomenological 1/Q 2 -corrections to R=σ L /σ T and F 2 found in QCD fits to the data. In particular, the rise of R at low Q 2 can be obtained from instanton-type vacuum fluctuations at a low scale.