Clownfishes are an iconic group of coral reef fishes, especially known for their mutualism with sea anemones. This mutualism is particularly interesting as it likely acted as the key innovation that triggered clownfish adaptive radiation. Indeed, after the acquisition of the mutualism, clownfishes diversified into multiple ecological niches linked with host and habitat use. However, despite the importance of this mutualism, the genetic mechanisms allowing clownfishes to interact with sea anemones are still unclear. Here, we used a comparative genomics and molecular evolutionary analyses to investigate the genetic basis of clownfish mutualism with sea anemones. We assembled and annotated the genome of nine clownfish species and one closely related outgroup. Orthologous genes inferred between these species and additional publicly available teleost genomes resulted in almost 16,000 genes that were tested for positively selected substitutions potentially involved in the adaptation of clownfishes to live in sea anemones. We identified 17 genes with a signal of positive selection at the origin of clownfish radiation. Two of them (Versican core protein and Protein O-GlcNAse) show particularly interesting functions associated with N-acetylated sugars, which are known to be involved in sea anemone discharge of toxins. This study provides the first insights into the genetic mechanisms of clownfish mutualism with sea anemones. Indeed, we identified the first candidate genes likely to be associated with clownfish protection form sea anemones, and thus the evolution of their mutualism. Additionally, the genomic resources acquired represent a valuable resource for further investigation of the genomic basis of clownfish adaptive radiation.