Background and Objectives: Non-small cell lung cancer (NSCLC) is histologically divided into adenocarcinoma (AD) and squamous cell carcinoma (SCC). While Checkpoint kinase 1 (CHEK1) regulates the DNA damage response, its subtype-specific clinical impact in NSCLC remains unclear. We investigated the association of CHEK1 expression with clinicopathologic features and prognosis in AD and SCC. Materials and Methods: Transcriptomic and clinical data from 980 patients (492 AD, 488 SCC) were analyzed using The Cancer Genome Atlas (TCGA). Patients were stratified by median CHEK1 mRNA expression. Relationships between expression and clinicopathologic variables were evaluated via Chi-square tests, and overall survival (OS) was assessed using Kaplan–Meier analysis. Results: In AD, high CHEK1 expression significantly correlated with advanced T stage (p < 0.001), lymph node metastasis (p = 0.025), younger age (p = 0.017), and shorter OS (p = 0.025). Conversely, CHEK1 expression in SCC did not reach statistical significance for survival outcomes, although a borderline trend was observed (p = 0.067). Conclusions: CHEK1 is a subtype-specific prognostic biomarker for AD but not for SCC. These findings suggest that CHEK1 overexpression reflects tumor aggressiveness in AD, highlighting its potential as a therapeutic target for this specific population.