An 8-week feeding trial was conducted to study the effect of long-term low-salinity stress on the growth performance, and expression of osmolarity and metabolism-related genes (Na+-K+-ATPase α-subunit and in gills, trypsin and chymotypsin in hepatopancreas) in white shrimp (L. vannamei). Four groups of the white shrimp (mean initial weight, 0.31±0.02g) were cultivated at salinity of 2, 10, 20 and 30psu for 8-week. All treatments were conducted in triplicate of 40 each. The results indicated that shrimps reared at salinity 20psu and 30psu were significantly higher in final weight, weight gain and specific growth ratio than the other treatments (p<0.05 when compared to 2 and 10), and those reared at salinity 2psu were significantly lower than the other treatments in growth performance and survival (p<0.05 when compared to other treatments). Quantitative real-time PCR (qRT-PCR) results indicated that Na+-K+-ATPase α-subunit and carbonic anhydrase mRNA levels at salinity 2psu and 10psu were increased significantly 1.79-, 1.65-fold and 3.22-, 2.31-fold respectively according to salinity 20psu, chymotrypsin and trypsin mRNA level at salinity 10psu and 2psu decreased significantly 15%, 36% and 72%, 45% respectively according to salinity 30psu. In conclusion, low salinity could, to some extent, reduce growth performance and survival significantly, and influence transcript levels of Na+-K+-ATPase α-subunit, carbonic anhydrase in gills and chymotrypsin, trypsin in hepatopancreas.