DeoxyriboNucleic Acid (DNA) encryption is a new encryption method that appeared along with the research of DNA nanotechnology in recent years. Due to the complexity of biology in DNA nanotechnology, DNA encryption brings in an additional difficulty in deciphering and, thus, can enhance information security. As a new approach in DNA nanotechnology, DNA strand displacement has particular advantages such as being enzyme free and self-assembly. However, the existing research on DNA-strand-displacement-based encryption has mostly stayed at a theoretical or simulation stage. To this end, this paper proposes a new DNA-strand-displacement-based encryption framework. This encryption framework involves three main strategies. The first strategy was a tri-phase conversion from plaintext to DNA sequences according to a Huffman-coding-based transformation rule, which enhances the concealment of the information. The second strategy was the development of DNA strand displacement molecular modules, which produce the initial key for information encryption. The third strategy was a cyclic-shift-based operation to extend the initial key long enough, and thus increase the deciphering difficulty. The results of simulation and biological experiments demonstrated the feasibility of our scheme for encryption. The approach was further validated in terms of the key sensitivity, key space, and statistic characteristic. Our encryption framework provides a potential way to realize DNA-strand-displacement-based encryption via biological experiments and promotes the research on DNA-strand-displacement-based encryption.