<p>Reactive species (RS), pivotal mediators in physiological and pathological processes such as cell death regulation and immune modulation, exhibit context-specific biological activities with significant interest in biomedical and industrial applications. Plasma simultaneously generates various types of RS and flexibly tuning their composition, providing a powerful approach for RS generation. However, instability and dynamic reactivity of RS limit precise control over composition, yield, and bioactivity, particularly in conventional plasma platforms, where ambient exposure compromises reproducibility and tunability. Here, we present a novel closed microplasma platform (CMP) integrated into a microfluidic device for selective, reproducible, and controllable generation of reactive oxygen species (ROS)- or reactive nitrogen species (RNS)-enriched plasma outputs. CMP enables robust switching between ROS- and RNS-dominant profiles by applying solution composition, specifically L-arginine availability, and leveraging stable gas-liquid interactions within a closed microfluidic environment. Biological validation confirms that ROS-dominant profiles induce caspase-3-mediated apoptosis, whereas RNS-dominant profiles trigger RIP3-dependent necroptosis, a form of immunogenic cell death (ICD). Notably, RNS-induced necroptosis exhibits hallmark ICD features, underscoring the potential of platform to engage antitumor immune responses. Indeed, P-Arg⁺ media showed antitumor efficacy and durable protective immunity in tumor-bearing immunocompetent mice, further enhanced by anti-PD-1. Therefore, we believe that the versatile CMP precisely orchestrates distinct RS to direct defined cell death programs, demonstrating translational potential for advanced plasma biomedicine and cancer immunotherapy.</p> Graphical Abstract <p></p>