Saline or salt water in the ocean accounts for 96.5% of total fresh water resource in the planet. Salinity isa global social and economic problem which severely inhibited plant growth and development. Utiliza-tion of marginal salt affected land and/or water resource becomes increasingly important because of theexplosion of world population and climate change. In this study, salt stress resistance of fifteen N. nuciferacultivars was firstly evaluated. The results showed that Welcoming Guests was the most resistant cul-tivar, while Hunan Lotus was the most sensitive one. Resistant cultivar Welcoming Guests accumulatedsignificant higher amount MDA and proline than Hunan Lotus prior to salt stress treatment, indicat-ing Welcoming Guests was pre-conditioned to salt stress. Salt sensitive lotus cultivar exhibited relativelower antioxidant enzyme activities and higher reactive oxygen species accumulation than resistant oneafter salt treatment. Since calcineurin B-like protein interaction protein kinase (CIPK)/SALT OVERLY SEN-SITIVE2 gene family played essential roles during plant salt stress response, three NnCIPK genes weresuccessfully cloned in this study. Phylogenetic analysis showed that these genes were high homologousto Arabidopsis and grape CIPK genes. Expression level analysis indicated that NnCIPK6 was highly inducedby NaCl treatment in resistant cultivar, while expression levels of NnCIPK14s showed fluctuation in sus-ceptible cultivar after salt treatment. These results partially characterized mechanisms of lotus salt stressresistance and provided useful information for utilization of lotus cultivars in salt water.