By using the next-to-leading order analyses of the precision lepton-hadron deep inelastic measurements at CERN and SLAC, we extract model independent constraints on the nucleon matrix elements of the twist-4 operators. We also study a parameterization of these matrix elements and point out the possibility that the matrix elements of the quark-gluon mixed operator has a negative value - (400 ± 100) MeV2 at 5 GeV2 renormalization scale. The uncertainty of our result due to the next-next-to-leading order correction is also discussed.