Lake eutrophication and cyanobacterial blooms have become worldwide environmental issues. Under cyanobacterial blooms (especially Microcystis), Daphnia spp. can transfer beneficial information to their offspring in order to improve adaptability. Hox genes are important regulatory factors of transcription in metazoans, and are involved in the growth and development of organisms. However, the mechanisms of Microcystis on the expression of Hox genes in Daphnia are unclear. In this study, the effects of Microcystis aeruginosa on Hox gene expression in the mothers and offspring (F1) of two Daphnia similoides sinensis clones were investigated using a mixed diet of M. aeruginosa and Scenedesmus obliquus. Compared with the 100%S food treatment, the survival rates at the end of the experiment of clone 1‐F1 in the food treatments containing M. aeruginosa were significantly lower, but it was significantly higher for clone 2‐F1 in the 20%M + 80%S food treatment. Moreover, the survival rates at the end of the experiment of clone 1‐F1 in the food treatments containing M. aeruginosa were significantly higher than those of their mother. Based on previous transcriptome data, 14 Hox genes of D. similoides sinensis were identified, including Abd‐B, CDX‐1, Dll, HOX‐1, HOX‐2, HOXA1, HOXA2, HOXB3, HOXB3‐2, HOXB7, HOXC4, HOXC7, HOXC8, and HOXD10. The expressions of Abd‐B, HOX‐2, HOXA1, HOXC7, and HOXD10 of clone 2‐mothers in the 40%M + 60%S food treatment were 2.9–22.5 times as high as in the 100%S food treatment, whereas the expressions of CDX‐1, HOX‐1, HOXB3, and HOXD10 of clone 1‐mothers were 4.8–13.1 times at same food level. The expression of HOXA2, HOXC7, HOXC8, and HOXD10 of clone 1‐F1 in the 40%M + 60%S food treatment was 8.2–21.1 times as high as in the 100%S food treatment. However, compared with the 100%S food treatment, the expressions of CDX‐1 in the mothers and F1 of clone 2 and HOXB7 in the mothers of clone 1 in the food treatments containing M. aeruginosa were significantly lower (p < .05). Our results suggest that the offspring (F1) produced by D. similoides sinensis mother pre‐exposed to toxic M. aeruginosa had stronger adaptability to M. aeruginosa than their mothers. Moreover, Hox gene expressions of D. similoides sinensis had obvious differences between clones under stress of toxic M. aeruginosa.