Oral squamous cell carcinoma is the most common malignancy of the oral neoplasm, comprising for more than 90 % of all oral malignancies, as well as approx. 38 % of head and neck tumors. So, it is of great significance to fiend the potential therapeutic target of the disorder. The messenger RNA and micro RNA expression profiling was performed for oral squamous cell carcinoma patients; micro RNA-messenger RNA regulatory network was established; the functions of potential micro RNA and messenger RNA were further explored in Cal27 oral adenosquamous carcinoma cell line. Compared with normal mucosa, oral squamous cell carcinoma patients demonstrated 192 differentially expressed genes (66 were up-regulated and 126 were downregulated) and 23 differentially expressed micro ribonucleic acids (4 were up-regulated and 19 were downregulated), among which micro RNA-196a and annexin-A1 were significant and differentially expressed. The annexin-A1 was a direct target of micro RNA-196a supported by bioinformatics and luciferase anal. The antagomiR-196a technique was utilized to silence the expression activity of micro RNA-196a. By this, micro RNA-196a was shown to modulate oral squamous cell carcinoma cellular migration, invasion and colony formation through annexin-A1. At the same time, the functions of micro RNA-196a and annexin-A1 were closely associated with protein kinase B and mitogen-activated protein kinase signaling pathways. This integrated study hypothesized a micro RNA-196a dependent signaling axis for oral squamous cell carcinoma and provided a beneficial reference for future clin. study.