SMARCA4 mutations are common in Medulloblastoma but not much is understood about its pathobiology. In this study we prepared SMARCA4 knockdown models using a Group 3 medulloblastoma cell line called HDMB03 and investigated the proteomic changes. We performed both DDA and DIA analyses and found that DIA performed better for our study. Our findings highlight that SMARCA4 loss disrupts proliferative and chromatin-regulatory networks while inducing metabolic reprogramming in vitro Group 3 MB.