Although SNRPE is a core spliceosomal component that guides pre-mRNA splicing in eukaryotic cells, its impact on mammary carcinoma prognosis and the immune microenvironment remains unclear. Pyroptosis, an inflammatory cell death, exerts tumor-suppressive functions and elicits antitumor immunity. Understanding the pathways that control pyroptosis will aid in developing specific antitumor strategies, while the relationship between SNRPE and pyroptosis has not been studied. To determine the impact of SNRPE on tumor prognosis, survival analysis and immune infiltration assessment were performed on clinical samples from patients with breast cancer. The antitumor effects and further mechanisms of SNRPE targeting were investigated via the xenograft murine model and cell biology experiments. Here, we found that upregulation of SNRPE expression was associated with unfavorable tumor prognosis and low levels of immune infiltration. Our data identified SNRPE targeting activated natural killer (NK) cell-mediated antitumor immunity in breast cancer by triggering pyroptosis of tumor cells . SNRPE targeting modulated pyroptosis of tumor cells in a ROS-dependent manner. This study contributes to new insights into the interaction between spliceosome-targeted tumors and host immunity, highlighting the targeting of spliceosome to trigger pyroptosis as a comprehensive therapeutic strategy for enhanced antitumor immunity in breast cancer.