Objective To detect the expression and clinical significance of POLD1 gene in non-small cell lung cancer (NSCLC) via bioinformatics method. Methods The expression difference of POLD1 in NSCLC tissue and normal lung tissue was investigated by TIMER database. UALCAN database was used to further verify different expression of POLD1 as well as the relationship between POLD1 expression and clinicopathological characteristics of NSCLC. The correlation between POLD1 gene and prognosis of NSCLC patients was detected by GEPIA and TIMER database. cBioPortal database was used to analyze frequencies of POLD1 gene mutation. POLD1-related protein-protein interaction network was constructed by STRING database. The relationship between POLD1 and immune infiltration was based on TISIDB database. Results The expression of POLD1 gene in lung adenocarcinoma and lung squamous cell carcinoma was significantly higher than that in normal lung tissue. In lung adenocarcinoma, patients with lower POLD1 level showed better prognosis. 1.2% of lung adenocarcinoma patients and 1.8% of lung squamous cell carcinoma patients carried mutated POLD1 gene, mainly missense mutations. POLD1 may interact with POLD2, POLD3, POLD4, POLE, RPA1, PCNA, MSH6, MSH2 and FEN1. The biological processes include DNA replication, mismatch repair, etc. Besides, the expression of POLD1 in NSCLC was correlated with the number of different immune cells. Conclusions The POLD1 gene is highly expressed in NSCLC patients, and negatively related with survival prognosis in patients of lung adenocarcinoma. POLD1 gene may be a potential diagnostic target and prognostic marker in NSCLC.