Albumin-bound paclitaxel (nab-PC) and docetaxel both produced favorable efficacy and safety as first-line therapy in advanced non-small cell lung cancer (NSCLC). However, the comparison between nab-PC and docetaxel remained unclear until now. This retrospective study aimed to compare the efficacy and safety of nab-PC/cisplatin with docetaxel/cisplatin as first-line therapy in advanced NSCLC. 271 patients with advanced NSCLC, who received either nab-PC (55 patients) or docetaxel (216 patients) were reviewed from 2012 to 2016. The primary endpoint was objective overall response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety profiles. Nab-PC presented a significantly higher ORR than docetaxel (47.3% vs 31.9%; P = 0.033). The difference of ORR was more significantly remarkable in patients with squamous histology (58.3% vs 29.0%; P = 0.007). Additionally, the DCR of nab-PC was significantly higher than docetaxel. Patients in nab-PC group had a trend toward improved PFS and OS compared with patients in docetaxel group, but this didn't reach statistical significance. Grade ≥ 3 neutropenia was less in nab-PC group, while Grade ≥ 3 anemia and thrombocytopenia were less in docetaxel group. Nab-PC/cisplatin as first-line therapy, produced significantly higher efficacy and reduced neutropenia than docetaxel/cisplatin in advanced NSCLC.