MicroRNAs (miRs) serve an essential role in tumorigenesis and are able to act as tumor suppressor genes or oncogenes. miR‑106a has been identified generally as an oncogene in multiple types of human cancer; however, its association with osteosarcoma has not previously been understood. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was used to detect miR‑106a expression in 18 osteosarcoma tissues compared with paired non‑cancerous adjacent tissues as well as osteosarcoma cell lines (U2OS, Saos‑2 and MG63) compared with a normal osteoblast cell line (hFOB1.19). The biological function of U2OS cells was assessed by using a Transwell cell invasion assay, MTS proliferation assay and flow cytometric analysis following the transfection with lentivirus‑mediated small interfering RNA (miR‑106a‑inhibitor). Western blotting and Luciferase reporters were used to investigate whether VNN2 was a target of miR‑106a in osteosarcoma cells. Based on the RT‑qPCR data, miR‑106a was significantly upregulated in osteosarcoma tissues and osteosarcoma cell lines compared with their control counterparts (P<0.01). The knockdown of miR‑106a resulted in cell proliferation and invasion inhibition. Furthermore, apoptosis enhancement and G2/M cell cycle arrest were detected by flow cytometry. The western blot analysis indicated that U2OS cells infected with miR‑106a‑inhibitor lentivirus had a higher VNN2 protein expression level compared with cells infected with miR‑106a‑negative control lentivirus. Luciferase reporters containing the 3'‑untranslated region sequence of VNN2 messenger RNA demonstrated VNN2 may be a target of miR‑106a. In addition, a negative correlation was confirmed between the expression of VNN2 and miR‑106a in the tumor samples. The results of the present study indicate that the knockdown of miR‑106a overexpressed VNN2 to inhibiting the proliferation, migration and invasion as well as inducing the apoptosis of human osteosarcoma cells.