MAPK1 signaling pathway promotes development and survival of epithelial tissue. MAPKs family controls the activity of microenvironment by triggering the intracellular signaling. Present study was designed to understand the MAPK1 PPI by using STRING database and retrieve top twenty interaction network to analyze the significance of MAPK1 related proteins in lung Squamous cell carcinoma (SqCC). A cancer platform, cBioPortal was used to perform gene alteration analysis to uncover their participation in lung SqCC progression. TP53 gene showed high ratio alteration among eleven lung SqCC linked disease causing MAPK1 mediated pathway genes in comparative study of lung squamous cell carcinoma TCGA, nature 2012 dataset. In present study, using meta-analysis, it has been characterized that vital MAPK1 signaling pathway altered interactions that are MYLK, BCL2, TP53, BCL6, RAF1, CTTN, FGF19, FGF3, FGF4, ATR, TP63, HES1, CDKN2A, RASA, MRAS, TNFSF10, IL12A, TEK, PTEN, AGTR1, DVL3, EPHB1, TRIO, RPS6KA1, RPS6KA2, FOS, FGFR1, PAK2, PRKCI, PIK3CA, PIK3CG and KDR. These are involved in cell proliferation, growth, differentiation, tumor suppressed activities and apoptosis. In aberrant conditions they act as oncogenic and anti-apoptotic agents. The empirical validation of MAPK1 signaling cascade key interactions in lung SqCC may give fruitful selection of therapeutic targets for squamous cell carcinoma in future.