Objective To explore the relationship between the curative effect and peripheral blood CYFRA21-1 and SCCA expression level in lung squamous carcinoma patients before and after chemotherapy. Methods The plasma CYFRA21-1 and SCCA levels in lung cancer patients before and after chemotherapy were evaluated by electrochemical luminescence method. 99mTc-MDP SPECT bone imaging was used to detect the tumor lesion size and number before and after therapy. The curative effect was classified as complete remission (CR), partial response (PR), stable classification (SD) and development (PD) based on SPECT imaging. The treatment was classified clinical benefit (CB) group including CR and PR, the invalid treatment (NR) group including PD and SD. Results There were significant difference on CYFRA21-1 and SCCA levels in lung cancer between CB group and NR group (P < 0.01). The SPECT imaging showed that 17 cases had lesions disappeared or reduced and 23 cases had no change or progress after treatment. Among 16 cases of high CYFRA21-1 level group after treatment, the clinical benefit (CB) was 18.75%; In 24 cases of low CYFRA21-1 level group, the CB and NR were 58.33% and 41.67% respectively. Among 14 cases of high SCCA level group after treatment, the clinical benefit (CB) was 21.43%; In 26 cases of low SCCA level group, the CB and NR were 53.85% and 46.15% respectively. Conclusion The detection of plasma CYFRA21-1 and SCCA levels in lung cancer patients before and after chemotherapy could have an important value in evaluation of treatment effect.