Thyroid transcription factor-1 (TTF-1) expression in patients with non-squamous non-small cell lung cancer (NS-NSCLC) is reportedly useful in selecting treatment regimens and predicting life expectancy. However, only a few studies have reported the association between TTF-1 expression and the efficacy of the current first-line regimens containing immune checkpoint inhibitors. It is unclear whether TTF-1 can be a hematologic toxicity indicator in patients receiving these treatment regimens. Patients who received the three-drug combination regimen of carboplatin, pemetrexed, and pembrolizumab, i.e., KEYNOTE-189, between April 2019 and December 2021 at Tsuyama Chuo Hospital and who had known TTF-1 expression were retrospectively studied using electronic medical records. Among the seven patients included, four patients were TTF-1 positive, while three were TTF-1 negative. TTF-1-positive patients showed a trend toward improved progression-free survival and were more likely to experience thrombocytopenia than the TTF-1-negative patients. These results suggest that TTF-1 expression in patients with NS-NSCLC could play a role in determining both treatment efficiency and hematologic toxicity.