Salinity is one of the most important environmental factors affecting the growth and development of sea cucumbers. microRNAs (miRNAs) can regulate the expression of their target genes by specifically binding to target mRNA. The expression profiles of Aja-miR-22 and Aja-miR-27, and two target genes, were detected in sea cucumbers that were under low salt stress. RNA and miRNA were extracted from coelomocytes of sea cucumbers in normal salinity seawater and were, after 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h exposure to salinity stress, analyzed by qRT-PCR. The results showed that the expression profile of Aja-miR-22 was consistent with that of Aja-miR-27 at each time point after initial salinity stress. Two miRNAs were induced to up-regulate and reached maximum expression at 3 h after stress. The expression maximums of Aja-miR-22 and Aja-miR-27 were 36 times and 16 times more than in the control group, respectively. The expression levels of Aja-miR-22 and Aja-miR-27 were higher than those of the control group under salinity stress, and Aja-miR-22 was significantly different from the control group at 3 h and 48 h after initial stress exposure (<0.01). Aja-miR-27 was significantly different from the control group at 3 h, 48 h, and 72 h under salinity stress. The expression of the target gene echinoderm microtubule-associated protein (EMAP; 77 kD) was also consistent with the general transcription factor IIE subunit 2, which reached the minimum value at 3 h under salinity stress. The expression level of EMAP was lower than that of the control group at each time point after salinity stress. The general transcription factor IIE subunit 2 (General Transcription Factor IIE Subunit 2) was significantly different from the control group at 48 h and 72 h under salinity stress (<0.01). The expression trends of Aja-miR-22 and Aja-miR-27 were negatively correlated with their target gene expression patterns before 24 h. The above results indicated that Aja-miR-22 and Aja-miR-27, and their corresponding target genes, are involved in the salinity adaptation mechanism of sea cucumber.