Based on orthogonal Latin cubes, an image cryptosystem with confusion–diffusion–confusion cipher architecture has been proposed recently (Inf. Sci.2019, 478, 1–14). However, we find that there are four fatal vulnerabilities in this image cryptosystem, which leave open doors for cryptanalysis. In this paper, we propose a reference-validation inference algorithm and design screening-based rules to efficiently break the image cryptosystem. Compared with an existing cryptanalysis algorithm, the proposed method requires fewer pairs of chosen plain-cipher images, and behaves stably since different keys, positions of chosen bits and contents of plain images will not affect the cryptanalysis performance. Experimental results show that our cryptanalysis algorithm only requirespairs of chosen plain-cipher images, whererepresents the image’s resolution. Comparative studies demonstrate effectiveness and superiority of the proposed cryptanalysis algorithm.