microRNAs (miRs) are endogenous noncoding RNAs that participate in a variety of cellular processes by regulating multiple targets to promote or inhibit cell behaviors. Emerging evidence suggests that miR-761 plays important roles in human cancers to function as either a tumor suppressor gene or an oncogene. However, its biological role in osteosarcoma (OS) remains largely elusive. This study found the expression of miR-761 was significantly reduced in OS tissues and cell lines. CXC receptor-1 (CXCR1), an oncogene which was overexpressed in a variety of human cancers including OS, was identified as a novel target of miR-761 using bioinformatic, luciferase reporter, and western blot analyses. Cell function assays revealed that miR-761 could inhibit cell proliferation and invasion at least partially through targeting CXCR1. Collectively, our present study suggested that miR-761 may be a promising treatment biomarker for OS.