In the present work, weighted Lp-norms of derivatives are studied in the spaces of entire functions \(\mathcal{H}\) p(E) generalizing the de Branges spaces. A description of the spaces \(\mathcal{H}\) p(E) such that the differentiation operator \(\mathcal{D}\) : F ↦ F′ is bounded in \(\mathcal{H}\) p(E) is obtained in terms of the generating entire function E of the Hermite-Biehler class. It is shown that for a broad class of the spaces \(\mathcal{H}\) p(E), the boundedness criterion is given by the condition E′/E ∈ L∞(ℝ). In the general case, a necessary and sufficient condition is found in terms of a certain embedding theorem for the space \(\mathcal{H}\) p(E); moreover, the boundedness of the operator \(\mathcal{D}\) depends essentially on the exponent p. We obtain a number of conditions sufficient for the compactness of the differentiation operator in \(\mathcal{H}\) p(E). Bibliography: 20 titles.