Abstract: Objective To observe the effects and mechanisms of Xiaoaiping combined with thermotherapy on gefitinib-resistance lung adenocarcinoma cell line A549,to provide theory evidence in thermochemotherapy for clinic. Methods The cultivated gefitinib-resistance lung adenocarcinoma cell line A549 was treated with ①5% CO₂,37 ℃ training;②to join xiaoaiping;③5% CO₂,42 ℃ culture;④5% CO₂,42 ℃ joint xiaoaiping.MTT assay was applied to analyze the inhibiting effects on the proliferation of A549 cells;RT-PCR,ELISA was performed to detected the content of VEGF,bFGF. Results The inhibition rate is 12% for Xiaoaiping,the inhibition rate is 12% for temperature 42 ℃,the inhibition rate is 45% for Xiaoaiping combined thermochemistry group,significant differences were observed(P＜0.05),so Xiaoaiping combined thermochemistry group have higher inhibiting effects on the proliferation compared Xiaoaiping,Thermochemistry group;the expression of VEGF is 78.95% for Xiaoaiping,the inhibition rate is 37.02% for temperature 42 ℃,the inhibition rate is 24.82% for Xiaoaiping combined thermochemistry group,significant differences were observed(P＜0.05);The protein expression of VEGF was 60.87%,4.78%,and 0.35%,respectively,significant differences were observed(P＜0.05),while the bFGF has no significant difference.There was an decreased expression of VEGF,bFGF and stronger inhibition of VEGF protein expression in Xiaoaiping combined thermochemistry group compared with Xiaoaiping,Thermochemistry group. Conclusion Xiaoaiping combined thermochemistry could reverse NSCLC resistance by reducing VEGF protein expression mediated tumor angiogenesis,thus inhibit tumor cell proliferation.