Simple Summary: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is an advanced magnetic resonance imaging (MRI) technique able to distinguish true diffusion from microcirculation-related perfusion without the use of contrast medium. Immunohistochemical analysis is the gold standard method to assess the programmed death-ligand 1 protein (PD-L1) expression status in patients affected by non-small cell lung cancer (NSCLC) to guide immunotherapy. We present our preliminary results on the evaluation of IVIM-DWI parameters and their correlation with the PD-L1 expression status in patients affected by stage III NSCLC. Since PD-L1 expression is very heterogeneous in NSCLCs, and an invasive biopsy of the tumor is necessary for immunohistochemical analysis, a non-invasive alternative method to quantify PD-L1 expression should be considered to provide information on the whole tumor. In the future, IVIM-DWI parameters could offer the possibility to perform diagnosis, pathological classification, to guide therapy, and to assess therapeutic responses. This study aims to investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) parameters in magnetic resonance imaging (MRI) and programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC). Twenty-one patients diagnosed with stage III NSCLC from April 2021 to April 2022 were included. The tumors were distinguished into two groups: no PD-L1 expression (<1%), and positive PD-L1 expression (≥1%). Conventional MRI and IVIM-DWI sequences were acquired with a 1.5-T system. Both fixed-size ROIs and freehand segmentations of the tumors were evaluated, and the data were analyzed through a software using four different algorithms. The diffusion (D), pseudodiffusion (D*), and perfusion fraction (pf) were obtained. The correlation between IVIM parameters and PD-L1 expression was studied with Pearson correlation coefficient. The Wilcoxon–Mann–Whitney test was used to study IVIM parameter distributions in the two groups. Twelve patients (57%) had PD-L1 ≥1%, and 9 (43%) <1%. There was a statistically significant correlation between D* values and PD-L1 expression in images analyzed with algorithm 0, for fixed-size ROIs (189.2 ± 65.709 µm²/s × 104 in no PD-L1 expression vs. 122.0 ± 31.306 µm²/s × 104 in positive PD-L1 expression, p = 0.008). The values obtained with algorithms 1, 2, and 3 were not significantly different between the groups. The IVIM-DWI MRI parameter D* can reflect PD-L1 expression in NSCLC. [ABSTRACT FROM AUTHOR]