The effects of salinity, Na/K ratio and their interaction on growth, molting, nutrient retention and food conversion of Litopenaeus vannamei were investigated. The test shrimp were reared in artificial seawater and fed fresh polychaete worms, Neanthes japonica (Izuka) for 30 days. Two salinities (30 and 15 ppt) and 5 Na/K ratios (25.6, 34.1, 47.3, 102.1 and 153.3, mmol/mmol) were set, and each treatment had four replicates. During the feeding trial, the molting frequency (MF) was affected by neither salinity nor interaction effects, but Na/K ratio had an effect (P < 0.05). And there was a tendency that MF rose with the increment of Na/K ratio at both salinities. Final body weight, weight gain (WG) and specific growth rate (SGR) were significantly influenced by salinity, Na/K ratio and interaction effects (P < 0.05), whose mean values at salinity 15 ppt were significantly higher than those at 30 ppt. At 30 ppt, WGs and SGRs of shrimp exposed to Na/K ratio 34.1 and 47.3 were respectively more than 26% and 15% higher than of those exposed to the other ratios (P < 0.05), but no significant differences in growth were found among treatments at 15 ppt (P > 0.05). Na/K ratio and interaction effects significantly affected the nutrient retention (PR and ER), food conversion (FCE) and protein utility (PER) of the shrimp (P < 0.05), whereas salinity showed little impact. At 30 ppt, the PR and ER of shrimp exposed to Na/K ratio 153.3 were more than 30% lower than of those exposed to the other 4 ratios (P < 0.05); the FCEs of shrimp exposed to Na/K ratio 34.1 and 47.3 were more than 20% higher than of those exposed to Na/K ratio 25.6 and 102.1 (P < 0.05), and the FCE of shrimp exposed to Na/K ratio 153.3 was even lower (P < 0.05). At 15 ppt, no significant differences in FCE among treatments were found (P > 0.05). PER showed the similar tendency as FCE at both salinities. It was indicated that the shrimp were more adaptable to abnormal Na/K ratios at low salinity than at higher salinities, and good growth could always be obtained within a Na/K range of 34.1–47.3 (mmol/mmol) regardless of salinity.