• An image encryption scheme with 2D discrete cosine Stockwell transform and DNA-level modulus diffusion is proposed. • The 2D discrete cosine Stockwell transform performs better in image compression and anti-noise. • The improved global chaotic diffusion algorithm achieves a better diffusion effect. A new image encryption scheme is presented by combining six-dimensional non-degenerate discrete hyper-chaotic system, two-dimensional discrete cosine Stockwell transform with DNA-level modulus diffusion. The significant advantages of this scheme are the large key space, strong anti-noise ability and resistance to common attacks. To resist the powerful chosen plaintext attack, the initial conditions of the chaotic systems are generated with the SHA-512 hash function value of the plaintext image and the external key. The transmission burden is reduced by compressing the original image with the two-dimensional discrete cosine Stockwell transform. Then random DNA encoding is performed on the compressed image to obtain the DNA image. To speed up the encryption, the DNA-level modulus diffusion algorithm is designed to scramble and diffuse pixels at the same time. Finally, the final encrypted image is obtained by re-encrypting the diffused DNA image with the bit-level permutation and the improved global dynamic diffusion. The two high-dimensional chaotic systems introduced in the image encryption scheme greatly increases the key space and then the image encryption scheme can resist the brute-force attack. The presented scheme is sensitive to both plaintext images and secret keys. Simulation results show that the proposed image encryption algorithm is feasible, secure and effective.