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Background Lung cancer (LC) is the most common form of cancer in the world. Of the proteins involved in cell differentiation and proliferation, the epidermal growth factor receptor (EGFR) is among the most significant. Amino acids play a crucial role in cell physiology as metabolic regulators. The benefits of liquid biopsies are their non-invasive nature, ease of collection, and ability to depict the entire tumor’s status. The present study is designed to detect the relation between the EGFR exon 19 747–750 deletion mutation and lung cancer and investigate the patterns of alterations of plasma-free amino acids (PFAA) in lung cancer patients of different histopathological types and stages as biomarkers for early detection of lung cancer. Methods The study sample comprised 60 lung cancer patients and 60 age- and sex-matched healthy individuals as the control group. Polymerase chain reaction and restriction fragment length polymorphism (PCR–RFLP) were used to examine the EGFR exon 19 747–750 deletion mutation, and an AA analyzer was used to quantify the plasma free amino acid (PFAA) profile. Results Compared with controls, LC patients had significantly higher levels of three AAs and significantly lower levels of fifteen AAs. Thirteen AAs varied significantly between stages I and II. In the lung cancer group, the percentage of cases of mutant EGFR exon-19 deletion increased to 30% from 13.3% in the control group. The histological forms of lung cancer did not significantly differ in this rise. Valine and citrulline plasma levels were substantially greater in the mutant than in the wild-type. Lysine, histidine, and methionine were the independent predictors of the LC group in multivariate analysis. Conclusion Lung cancer development is influenced by the EGFR exon 19 747–750 deletion mutation, and the prognosis and early prediction of lung cancer are greatly affected by the amino acid profile concentrations.