Abstract: Traditional encryption schemes are largely based on the two stepsconfusion and diffusion proposed by Shannon. It is proved by experiments that encryption designed on bit level is more efficient. An encryption scheme based on DNA coding, codon grouping and substitution is proposed in this paper, which belongs to bit level encryption. Original media is encoded into pseudo codon sequence with the ideology of DNA coding and central dogma in molecular biology. Then codons are grouped together with a random grouping method. After that, an arbitrary N-nary system is constructed with the pseudo codon sequence and the grouping strategy. Information that controls the substitution of codons is generated with a hyper-chaotic system and the arbitrary N-nary system. Finally, substitution of codons in the pseudo codon sequence is imposed to accomplish the encryption. Both theoretical analysis and experimental results show that the proposed method has much better performance.