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Steganography provides unconventional solutions to protect communication as well as copyright of intellectual property. In this paper, we propose a steganographic method that exploits some characteristics of the Deoxyribonucleic Acid (DNA) for hiding other types of digital content. The proposed work is an extension to [1], as it provides a solution to the problem that the sender and the receiver have to secretly communicate both the stego-DNA and the reference sequence. Communicating such information could be suspicious and reveals the secrecy of the steganographic channel itself. Thus, the proposed hiding method is implemented in two main stages: the first one hides the secret message into some reference DNA sequence using a generic substitution technique. The next phase employs a self embedding algorithm that randomly inserts the stego-DNA sequence into the reference one. In this way, the extraction process can be done blindly and the communicating parties don’t actually have to exchange anything in advance but the secret key. Furthermore, a DNA-based playfair ciphering is applied on the secret data before embedding in order to increase the security of the hiding algorithm. When compared with other hiding methods, the proposed method showed an outstanding performance providing high security and embedding capacity.

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