MicroRNAs are a family of non-coding RNAs, 22 nt in length, which repress gene expression by pairing to the 30 - untranslated regions of target mRNAs [1]. Aberrant expression of microRNAs in tumor cells contributes to tumor growth by the activation of cell proliferation, the induction of resistance to apoptosis and other related pathological process [2]. Using anti-miR oligonucleotides to inhibit onco-miRs has shown efficacies in tumor xenograft models and thus has great potential in cancer therapy [3]. Emerging evidence indicates that miR-494 plays a critical role in cancer development. The level of miR-494 was higher in a number of cancers such as classical Hodgkin’s lymphoma [4] and oral squamous cell carcinoma [5]. Anti-miR-494 treatment significantly diminished tumor size in mice with primary myc-driven liver tumor [6]. Recently, it was reported that knockdown of miR-494 in myeloid-derived suppressor cells, one of the most important cell types in tumor microenvironment, inhibited the growth of mouse breast cancer [7], indicating that miR- 494 may also promote cancer progression by modulating tumor microenvironment. Angiogenesis is an essential component in microenvironment to tumor growth and metastasis, whereas inhibiting angiogenesis has become a promising strategy for cancer therapy [8]. It has been reported that tumors can promote angiogenesis through different extracellular pathways, including cellular factors and microRNAs [9]. Therefore, we sought to examine a role of miR-494 in the tumor angiogenesis and demonstrated that miR-494 is a novel tumor-derived paracrine signal to promote angiogenesis and tumor growth under hypoxic condition.