Abstract: To explore the molecular mechanisms affecting the body shape differences in Hypophthamichthys nobilis, morphological different H. nobilis individuals with normal body shape (CK group) and with shortened body (PG group) were collected for transcriptome and miRNA sequencing analysis in this study. The results showed that a total of 25 327 unigenes and 8 325 miRNAs were obtained. 930 differentially expressed genes (DEGs) and 146 differentially expressed miRNAs (DEMs) were identified, including 473 up-regulated genes and 457 down-regulated genes, as well as including 44 up-regulated miRNAs and 102 down-regulated miRNAs, respectively. By comparing the DEGs and target genes of DEMs, 140 overlapped genes were obtained, which were mostly enriched in cell cycle (ko04110), DNA replication (ko03030), adhesion plaques (ko04510), and ECM receptor interaction (ko04512) signaling pathways. Additionally, 16 overlapped DEGs were identified to be involved in bone formation and development, such as exo1, mcm4, ccna2, smc2 and ccna2, which were hypothesized to be associated with H. nobilis body shape differences. In addition, through mRNA-miRNA interaction network analysis, DEGs including apob, tgfbr2a and col2a1b as well as DEMs including miR-34a-5p, miR-252a and miR-6547-5p were detected as core members in the network; these DEGs and DEMs may play important roles in regulating and maintaining the morphologically in H. nobilis. Validation experiments using qPCR revealed that the trends of relative expression differences between CK with PG groups were consistent with the RNA-Seq and sRNA-Seq data. These DEGs, DEMs, and enriched metabolic pathways identified in this study may be associated with H. nobilis body shape difference. This study may provide basic data for further exploration of the molecular mechanisms affecting body shape differences in H. nobilis.