Background: Yes-associated protein 1 (YAP1) is responsible for tumor growth, progression and metastasis. The mechanisms controlling the generation and relative ratio of the functional YAP1 and other co-factors are not well-understood. Various literature reported that co-factors like cytokines significantly influence signaling pathways to introduce epithelial immunity and regeneration, which later helps increase cancer-related phenotypes. Among various cytokines, IL-18 has emerged as a major player in inflammation and progression of different types of cancers. Till now, much information has not been known about the role of YAP1 in tumor aggressiveness and immune evasion in breast cancer with respect to IL-18. Aim: We aimed to explore the effect of YAP1 in tumor aggressiveness and immune evasion in breast invasive carcinoma and metastatic breast cancer in the context of Interleukin-18 (IL-18) in silico. Methods and Results: We used publicly available data generated by The Cancer Genome Atlas (TCGA) Research Network through cBioportal web platform. Kaplan–Meier method was used to determine the overall survival and comparison between curves were made using Log-Rank test. The p values were determined by Fisher's exact test with the null hypothesis. Correlation plots were analyzed by comparison with gene copy numbers from the GISTIC2.0, available through cBioportal. Our analyses suggest that IL-18 influences YAP1 expression in breast oncogenesis via Interferon-gamma (IFN-γ) production. Patients having a higher expression of IL-18 possess a better prognosis and higher YAP1 expression with lower IL18 drives to poor clinical results in breast cancer. Conclusion: This can provide new approaches to better understand the relation between YAP1 and IL-18 in breast cancer progression by performing in vitro and in vivo studies. Also, IL-18 can be considered as a potential target for tumor treatment in YAP1 overexpressed breast carcinoma. © 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.