Oral squamous cell carcinoma (OSCC) is a malignant disease in the world which has a profound effect on human health and life quality. According to tumor stage and pathological diagnosis, OSCC is mainly treated by combinations of surgery, radiotherapy and chemotherapy. However, traditional treatment methods suffer from some limitations, such as systemic toxicity, limited therapeutic effect and drug resistance. With the rapid development of nanotechnology, nanodrug delivery systems (DDSs) and intelligent DDSs have been widely used in targeted therapy for OSCC. Meanwhile, the newly developed therapeutic techniques such as immunotherapy, gene therapy and bionic technology provide the possibility to realize the active targeted therapy. Here, the latest advances of target therapy for OSCC are reviewed, and their therapeutic remarks, current limits and future prospects are also systematically interpreted. It is believed that active and passive targeted therapies have great potentials for clinical transformation and application of OSCC, which will greatly improve human quality of life.