Objective: To investigate the sensitivity of novel small molecule tyrosine kinase inhibitors NXGH and NXGF to 4 lung cancer cell lines with different EGFR expression and mutant status. Methods: Novel small molecule tyrosine kinase inhibitors NXGH and NXGF based on NXG structure were designed. Four lung cancer cell lines with different EGFR expression and mutation status: PC9(Exon 19 deletion mutation), H1975(L858R mutation combined T790M mutation), H358(wide EGFR expression) and H520(EGFR negative expression) were chosen. Inhibition ratio of NXGH and NXGF at different concentration (1.25,2.5,5.0,10,20,30,40,60,80 μmoL·L-1)against 4 lung cancer cell lines in 48 h were investigated by MTT method.IC50 and cell viability were calculated,and sensitivity between different cell lines were compared. Results:IC50 of PC9, H358, 520 and H1975 cells incubated with NXGH were 0.675 μ moL·L-1,12.097 μmoL·L-1,11.368 μmoL·L-1 and 0.981 μmoL·L-1, respectively. IC50 of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25, 2.5 and 5 μmoL ·L-1 (P＜0.05). IC50 of PC9, H358, H520 and H1975 cells incubated with NXGF were0.685 μmoL·L-1, 4.265 μmoL·L-1, 3.097 μmoL·L-1 and 0.331 μmoL·L-1, respectively. IC50 of PC9 and H1975 were less than H358 and H520 when the concentration was 1.25 and 5 μmoL·L-1 (P＜0.05). Conclusion: The novel small molecule tyrosine kinase inhibitors NXGH and NXGF, which were designed and constructed in our laboratory successfully, had high affinity for lung cancer cells with different EGFR expression and mutation status. And they were more sensitive to EGFR mutant cell at low concentration as expected. [ABSTRACT FROM AUTHOR]