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The aim of this study was to evaluate the expression of PIK3CA and survivin in adenosquamous lung cancer (ASC) patients and their clinicopathological significance. A total of 32 patients with adenosquamous carcinoma and ten cases of normal lung lesion were investigated, and the expressions of PIK3CA and survivin were detected by immunohistochemistry. The PIK3CA and survivin expression in adenosquamous lung carcinoma tissues was significantly higher than those of the normal lesions (p = 0.02). The positive rate of PIK3CA and survivin expressions was in accordance with the tumor-node-metastasis stage (p = 0.002/0.013), pathological grade (p = 0.019/0.013), and lymph node metastasis (p = 0.029/0.008). Out of 15 patients with definite follow-ups, highly positive expressions of PIK3CA (12 cases) and survivin (11 cases) were suggested to be associated with adverse prognosis (nine cases recurrence and four cases died). A positive correlation was also observed between the expressions of PIK3CA and survivin (r = 0.622, p< 0.001). These findings indicated that PIK3CA and survivin up-regulation might play an important role in lymph node metastasis and adverse prognosis in ASC. Nevertheless, further additional prospective studies in the area of ASC molecular profiling are needed.