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Immunotherapy has lately become the most preferred cancer treatment method, and for non‐small cell lung cancer (NSCLC) first‐line treatment, there are many immunotherapy options. This study aimed to assess the effectiveness and toxicity of paclitaxel (PTX), docetaxel (DTX) chemotherapy, immune checkpoint inhibitor treatment (durvalumab; DVL), and their combination in NSCLC. A‐549 cells were treated with DVL in combination with PTX and DTX (a quarter of the IC50) to investigate their anticancer effects on these cells. The MTT assay, wound healing tests, and double‐staining with Annexin V/PI were used to assess the cell viability, apoptosis, and migration. The results showed that a combination of 0.35 mg/mL DVL with 6.5 μg/mL PTX and 1.75 μg/mL DTX produced a synergistic effect with CI values of 0.88, 0.37, and 0.81, respectively. Moreover, the PTX + DTX + DVL combination led to a significantly increased apoptotic rate up to 88.70 ± 3.39% in the A549 cell line compared to monotherapy (p <.001). In addition, we found that the combination therapy with these agents increased the expression level of Bax, Cas‐3, p53, and Bax/Bcl‐2 ratio in all experimental groups. In conclusion, the results suggest that combining anti‐PD‐L1 antibody therapy with chemotherapy may provide a promising approach to enhance treatment outcomes and be a potentially efficacious strategy for treating NSCLC patients. Further research and clinical investigations are needed to elucidate the underlying molecular mechanisms and validate the therapeutic potential of these compounds in vivo. Significance statement: In this study, durvalumab (DVL), an immune checkpoint inhibitor, has been proposed to evaluate the antitumor efficacy of the taxane family. The results illustrate that DVL improved taxane family‐mediated cytotoxicity in the non‐small cell lung cancer (NSCLC) cell line. The triple medication (paclitaxel [PTX], docetaxel [DTX], and DVL) combination therapy altered the cell proliferation in the NSCLC cells and showed a synergistic antitumoral effect, which contributes to taxane family‐mediated cell cycle arrest and apoptosis. The combination potential benefit in the NSCLC treatment is the study's most significant discovery. Combining PTX, DTX, and DVL increased apoptosis by activating apoptotic pathways, and arrested cells in the G2/M phase. Also, the triple medication combination significantly reduced cell migration and invasion. Our findings also point to the possibility of increasing the overall anticancer effectiveness of DTX or PTX in NSCLC by adding anti‐PD‐L1 treatment. [ABSTRACT FROM AUTHOR]