The aim of the present study was to investigate the molecular mechanism of nasopharyngeal carcinoma (NPC) primary tumor development through the identification of key genes using bioinformatics approaches. Using the GSE53819 microarray dataset, acquired from the Gene Expression Omnibus database, differentially expressed genes (DEGs) were screened out between NPC primary tumor and control samples, followed by hierarchical clustering analysis. The Search Tool for the Retrieval of Interacting Genes database was utilized to build a protein‑protein interaction network to identify key node proteins. In total, 1,067 DEGs, including 326 upregulated genes and 741 downregulated genes, were identified between the NPC and control samples. The results of the hierarchical clustering analysis demonstrated that 95% of the DEGs were sample‑specific. Furthermore, PDZ binding kinase (PBK), centromere protein F (CENPF), actin‑binding protein anillin (ANLN), exonuclease 1 (EXO1) and chromosome 15 open reading frame 42 (C15ORF42) were included in the obtained network module, which was closely associated with the cell cycle and nucleic acid metabolic process GO functions. The results of the present study revealed that EXO1, CENPF, ANLN, PBK and C15ORF42 may be involved in the mechanism of NPC via modulating the cell cycle and nucleic acid metabolic processes, and may serve as molecular biomarkers for the diagnosis of this disease.