Body scales in teleost fish are the first line of defense in protecting the fish from invading pathogens. However, the relationship between the adaptive evolution of immune-related genes and changes in the body scale-covering of fish has not been previously studied. Schizothoracine fish, characterized by progressive reduction of body scales from the primitive to the highly specialized species, are a good group to investigate this relationship. We obtained 11 IRF genes (IRF1–11) from 14 of schizothoracine fish representing primitive, specialized, and highly specialized species, of which seven IRF genes (IRF2, IRF3, IRF5, IRF6, IRF7, IRF8 and IRF9) contained the complete CDS. Sequence analysis demonstrated the deletion or insertion of 4–7 amino acids in IRF2, IRF3, IRF6 and IRF9, which seems to be a common phenomenon in the schizothoracine fish. Selection pressure analysis supported the hypothesis that positive selection has been driving the rapid evolution of IRFs in specific lineages of the schizothoracine fish. This, however, is not correlated with body scale reduction or loss in the evolution of these IRFs. Remarkably, the deletion or insertion found in IRF protein sequences presented a regular pattern corresponding to the scale-covering changes in schizothoracine fish. Our study provides evidence for positive selection in the IRF family, contributing to a better understanding of the adaptive evolution of immune-related genes in schizothoracine fish in response to environmental changes of the Qinghai-Tibetan Plateau.