Among 92 patients treated with crizotinib, 76.09% (70/92) developed acquired resistance, and 11.96% (11/92) had primary resistance...BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, PIK3CA mutations), SMARCA4 mutations or EML4-ALK fusion (non A20) might contribute to molecular mechanisms of primary resistance to crizotinib in ALK+NSCLC.