The aims of this study were to investigate the expression of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) and its relationship with clinicopathological features in lung cancer (LC), breast cancer (BC), and head and neck cancer (HNSC) and to discuss the possibility of being a potential diagnostic and prognostic biomarker. Data on the RNA expression profile, protein expression profile, and relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas databases. The relationship between mRNA expression and clinicopathological features was evaluated. Survival analysis was performed to assess overall survival (OS) and relapse-free survival (RFS). The multivariate Cox regression model was employed to analyze the independent prognostic factors. Finally, protein-protein interaction networks were constructed and enrichment analysis was performed to identify the latent P4HA1-related terms and pathways. This study showed that was upregulated in three types of tumor tissues ( < 0.05) and high was significantly relevant to the clinical features of patients with LC, BC, or HNSC. Survival analysis indicated that patients with high had unfavorable clinical outcomes. Multivariate analysis showed that the high expression was an independent prognostic factor for poor OS and RFS in LC and HNSC patients. Bioinformatic analysis was performed to predict P4HA1-interacted proteins and further evaluate possible signal pathways. In the current study, the rising was identified in LC, BC, and HNSC and significantly correlated with the clinicopathological features of patients. High , suggesting poor clinical outcomes, could be used as an early diagnostic and prognostic biomarker for patients with aforementioned tumors.