In the paper we use recently proposed cellular automata (CA) based methodology (Szaban and Seredynski in LNCS, vol. 5191, pp. 478-485, 2008) to design the 6 × 4 S-boxes functionally equivalent to S-boxes used in current cryptographic standard known as Data Encryption Standard (DES). We provide an exhaustive experimental analysis of the proposed CA-based S-boxes in terms of nonlinearity, autocorrelation, balance and strict avalanche criterion, and compare results with ones corresponding to DES S-boxes. We show that the proposed CA-based Sboxes have cryptographic properties comparable to or better than classical S-box tables. The interesting feature of the proposed S-boxes is a dynamic flexible structure fully functionally realized by CA, while the classical DES S-boxes are represented by predefined unchangeable table structures.