Objective: To explore and analyze the clinical efficacy and tumor markers of gefitinib targeted therapy in patients with non-small cell lung cancer. Methods: 92 patients with advanced non-small cell lung cancer admitted to our hospital from July 2022 to August 2024 were selected as the research subjects. According to the principle of random envelope drawing, the 92 patients were divided into a gefitinib group of 46 cases and a traditional group of 46 cases. The control group received conventional chemotherapy, while the gefitinib group received gefitinib treatment in addition to the control group treatment. Both groups were observed for 3 courses of treatment, and the efficacy and changes in serum carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCCA) expression were recorded. Results: After 3 courses of treatment, the total effective rate of the gefitinib group was 82.61%, while the control group was 52.17%. The gefitinib group was significantly higher than the control group (P<0.05). The incidence of toxic side effects such as rash, diarrhea, nausea and vomiting, and liver dysfunction during three treatment courses in the gefitinib group was 8.70%, 8.70%, 10.87%, and 6.52%, respectively, while in the traditional group it was 8.70%, 10.87%, 8.70%, and 6.52%, respectively. There was no significant change in the gefitinib group compared to the traditional group (P>0.05). After three treatment courses, the serum CEA and SCCA levels in both groups were significantly lower than before treatment (P<0.05), and the serum CEA and SCCA levels in the gefitinib group were also significantly reduced compared to the traditional group after three treatment courses (P<0.05). All patients were followed up until December 1, 2024, and there was no significant difference in follow-up time between the two groups (P>0.05). The recurrence rate of the gefitinib group was 2.17%, while that of the traditional group was 17.39%. There was a statistically significant decrease in the gefitinib group compared to the traditional group (P<0.05). Conclusion: The application of gefitinib targeted therapy in non-small cell lung cancer patients can improve the therapeutic effect without increasing the incidence of toxic side effects, and can also reduce the serum CEA, SCCA levels and recurrence rate of patients.