In this research, we found that the IL-33-induced Ro60 activation in KCs could be restrained by PI3K/Akt or NF-κB inhibition but upregulated after the inhibition of MAPK/ERK, which indicated that NF-κB and PI3K/Akt signaling pathways mediate the regulation of Ro60 by IL-33. The gene discussed is RO60; the disease is dry eye syndrome.