The “Cancer Immunoediting” concept has provided critical insights suggesting dual functions of immune system during the cancer initiation and development. However, the dynamics and roles of CD4+ and CD8+ T cells, CD19+ B cells, and CD56+ NK cells in the patients with oral squamous cell carcinoma during treatment remain unclear. A total of 43 patients with OSCC were divided into different groups according to different clinical factors (TNM staging, pathological patterns, age and genders) for assessment of relations with CD3+CD4+ T cells, CD3+CD8+ T cells, CD3−CD19+ B cells and CD3−CD16+CD56+ NK cells and different chemotherapy and radical operation. The expression of CD3+CD4+ T cells were significantly increased in advanced tumor stage, large tumor size and positive lymph nodes metastasis, compared to that in early groups. The accumulation of CD3+CD4+ T cells were significantly increased in OSCC patients received 2 cycles CT and radical operation. Moreover, the accumulation of CD3+CD8+ T cells were significantly decreased in OSCC patients received 2 cycles CT and radical operation. The distribution of circulating CD3−CD19+ B cells was related with radical operation in patients with OSCC. This study indicate that CD4+ T cells have opposing roles in OSCC progression and outcomes, which provides new insights relevant for the development of effective cancer immunotherapeutic approaches. 2 cycles TP regime chemotherapy and radical therapy may contribute to increase the effects of anti-tumor immunity on patients with OSCC.