INTRODUCTION: Non-small cell lung cancer (NSCLC) continues to pose a considerable health challenge with few therapeutic alternatives. Liquid crystalline nanoparticles (LCN) are nanostructured drug delivery systems made of lipid-based amphiphilic materials that self-assemble into crystalline phases in aqueous environments. LCN have become a promising way to treat NSCLC owing to their specific properties that make them useful for targeted delivery and controlled drug release. AREAS COVERED: The review provides a brief overview of the use of LCN in the treatment of NSCLC. It explores their composition, fabrication methods, and characterization processes. The article further addresses several nanoparticle-based approaches for the treatment of NSCLC. Ultimately, it underscores the promise of LCNs as a promising drug delivery system for NSCLC and discusses the obstacles and outlook in this field. EXPERT OPINION: LCN represents a promising frontier in the treatment of NSCLC, offering several specific advantages over conventional therapies. Utilizing their intrinsic self-assembly characteristics, LCN provides meticulous control over drug encapsulation, release kinetics, and cellular absorption, which are crucial for improving therapy success. LCN also has the capability for co-delivery of various drugs, facilitating synergistic therapeutic benefits and addressing multidrug resistance, a prevalent issue in NSCLC treatment.