Background Nab‐paclitaxel (nab‐PTX) has better transfer to tumor tissue than cremophor‐based paclitaxel. It suggests that the optimum dose of nab‐PTX might be lower than the dose and schedule that is widely used. We designed a randomized phase II trial to examine the clinical utility and safety of nab‐PTX in patients with previously treated advanced non‐small cell lung cancer (NSCLC). Methods Patients were randomly allocated (1:1) to receive nab‐PTX monotherapy at 100 mg/m2 (group A) or 70 mg/m2 (group B). The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results Finally, 81 patients were randomized. Similar results were observed in both groups for PFS (3.75 vs. 3.71 months), OS (13.50 vs. 16.13 months), or ORR (20.5% vs. 23.1%). The incidences of grade 3 or worse AEs were 57.5% in group A and 41.5% in group B. The proportion of serious side effects was 10.0% in group A and 4.9% in group B. Conclusion Both standard dose and low dose of nab‐PTX monotherapy are active for previously treated NSCLC patients with better safety profile. Therefore, nab‐PTX 70 mg/m2 dose and schedule in the trial would be a reasonable option. In this phase 2 randomized clinical trial to examine activity and safety, and to determine optimum dose of nab‐PTX in patients with previously treated stage IIIB/IV or postoperative relapsed NSCLC, both 100 and 70 mg/m2 of nab‐PTX monotherapy were active in patients with previously treated advanced NSCLC. Since the 70 mg/m2 dose has a better safety profile and numerically favored median overall survival, 70 mg/m2 on days 1, 8, and 15 every 4 weeks would be the optimal dose and schedule for nab‐PTX during treatment of NSCLC.