The development of visual organs is regulated in Bilateria by a network of genes where members of the Six and Pax gene families play a central role. To investigate the molecular aspects of eye evolution, we analyzed the structure and expression patterns of cognate members of the Six family genes in jellyfish (Cnidaria, Hydrozoa), representatives of a basal, non-bilaterian phylum where complex lens eyes with spherical lens, an epidermal cornea, and a retina appear for the first time in evolution. In the jellyfish Cladonema radiatum, a species with well-developed lens eyes in the tentacle bulbs, Six1/2-Cr and Six3/6-Cr, are expressed in the eye cup. Six4/5-Cr is mainly expressed in the manubrium, the feeding, and sex organ. All three Six genes are expressed in different subsets of epidermal nerve cells, possibly of the RFamide type which are part of a net connecting the different eyes with each other and the effector organs. Furthermore, expression is found in other tissues, notably in the striated muscle. During eye regeneration, expression of Six1/2-Cr and Six3/6-Cr is upregulated, but not of Six4/5-Cr. In Podocoryne carnea, a jellyfish without eyes, Six1/2-Pc and Six3/6-Pc are also expressed in the tentacle bulbs, Six1/2-Pc additionally in the manubrium and striated muscle, and Six3/6-Pc in the mechanosensory nematocytes of the tentacle. The conserved gene structure and expression patterns of all Cladonema Six genes suggest broad conservation of upstream regulatory mechanisms in eye development.