Non-small-cell lung cancer (NSCLC) is one of the most common lung cancers, and microRNAs (miRNAs) have been reported to play essential roles in NSCLC. Recent studies have indicated that miR-330-3p expression is up-regulated in NSCLC samples and in tissues of NSCLC brain metastasis. In this study, up-regulation of miR-330-3p expression was confirmed in NSCLC and 20 NSCLC patient samples. Furthermore, miR-330-3p was over-expressed in NSCLC cell lines A549 and H23, and the promotive function of miR-330-3p was investigated in regulating NSCLC cell proliferation and cell cycle distribution. To identify potential target genes of miR-330-3p in NSCLC, the miRNA target prediction databases were used. Luciferase activity assay and real-time RT-PCR analysis confirmed that miR-330-3p is negatively correlated with the expression of early growth response 2 (EGR2). Moreover, it was also found that EGR2 mRNA contains two potential binding sites for miR-330-3p. Knock-down of EGR2 with siRNA was demonstrated to have a similar effect as the over-expression of miR-330-3p in NSCLC cell lines. Taken together, our results show that EGR2 is a target of miR-330-3p.