The ASC-1 complex, consisting of TRIP4, ASCC1, ASCC2, and ASCC3, plays a pivotal role in regulating nuclear receptors and transcription factors that influence immunity, cellular proliferation, and apoptosis, and a multiomic analysis of ASCC1/2/3 was therefore performed to investigate its potential role on a pan-cancer scale. Although it has been implicated in DNA repair mechanisms and neurodegenerative diseases, its specific function within cancer biology remains poorly understood. This study conducted a pan-cancer analysis of ASCC1/2/3's roles in the tumorigenesis process and explored their regulatory effects on lung adenocarcinoma. We conducted a comprehensive analysis of 10,967 tumor samples across 30 distinct cancer types. It was found that alterations in ASCC1/2/3 occurred in 754 cases (7% of the patients analyzed), with ASCC3 being the most frequently altered at 4%. Furthermore, elevated expression levels of ASCC1/2/3 were observed in the majority of cancer types examined. Notably, the expression levels of ASCC1 and ASCC3 demonstrated a correlation with CD4-positive T cell infiltration. In vitro experiments demonstrated that the ASCC family effectively inhibited tumor proliferation, migration, and invasion in lung adenocarcinoma cell line. Our findings indicate a significant association between the ASCC family and tumors while providing a foundation for further investigation into its role in cancer biology and potential clinical applications.