The role of silent position in the codon on the protein structure is an interesting and yet unclear problem. In this paper, 563 Homo sapiens genes and 417 Escherichia coli genes coding for proteins with four different folding types have been analyzed using variance analysis, a multivariate analysis method newly used in codon usage analysis, to find the correlation between amino acid composition, synonymous codon, and protein structure in different organisms. It has been found that in E. coli, both amino acid compositions in differently folded proteins and synonymous codon usage in different gene classes coding for differently folded proteins are significantly different. It was also found that only amino acid composition is different in different protein classes in H. sapiens. There is no universal correlation between synonymous codon usage and protein structure in these two different organisms. Further analysis has shown that GC content on the second codon position can distinguish coding genes for different folded proteins in both organisms.