Porcine epidemic diarrhea virus (PEDV) is an enteric pathogen belonging to the family Coronaviridae that causes the porcine epidemic diarrhea, a highly contagious disease with high mortality in piglets and symptoms that include dehydration and severe diarrhea. Considering the high frequency of genetic mutations in PEDV and its potential for interspecies transmission, as it can infect and replicate in bat and human cells, a comprehensive analysis of its codon usage bias was performed. The effective number of codons (ENC) and the relative synonymous codon usage (RSCU) were determined, revealing codon usage bias in the PEDV genome. Principal component analysis (PCA), an ENC plot, and a parity rule 2 (PR2) plot showed that mutation pressure and natural selection have influenced the codon usage bias of the PEDV genomes. Correlation analysis with GRAVY and aromaticity values and neutrality plot analysis indicated that natural selection was the main force influencing the codon usage pattern, while mutation pressure played a minor role. This study provides valuable basic data for further fundamental research on evolution of PEDV.