MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. miR-192 and -215, which have the same "seed region", have not been comprehensively investigated using a large number of cases in gastric cancer. The total RNA was extracted from 118 gastric cancer tissues and three gastric cancer cell lines as well as matched non-tumor adjacent tissues (NATs). After polyadenylation and reverse transcription, expression levels of miR-192 and -215 were determined by real-time PCR and calculation using the 2(-∆∆CT) method for evaluation of the association between miR-192, and -215 expression levels and clinicopathological characteristics. There were no significant differences in miR-192 and -215 expression levels between gastric cancer tissues and non-tumor counterparts (both p > 0.05, paired t-test). Interestingly, miR-192 and -215 were down-regulated in MGC-803 cells, BGC-823 cells and SGC-7901 cells (all p < 0.01, paired t-test). Also, the down-regulation of miR-192 and -215 was demonstrated to be associated with increased tumor sizes (both p = 0.003, Mann-Whitney U test) and advanced Borrmann type tumors (p = 0.015 and p = 0.044, respectively, Kruskal-Wallis H test). Moreover, the expression of miR-192 was significantly lower in the pT4 stage of gastric cancer than in pT1, pT2 and pT3 stages (p = 0.026). Furthermore, there was a strong correlation between miR-192 and -215 in gastric cancer tissues (p < 0.001, Pearson regressions). miR-192 and -215 might be related to the proliferation and invasion of gastric cancer. Potentially, they could become important biomarkers.