Synonymous codons have different frequencies of usage in many species. Based on the frequency of usage, the codons can be divided into two groups, rare codons and abundant codons. Rare codons are found to be enriched at the start regions of genes, and it is assumed that these codons can reduce elongation speed of genes. However, the rare codon usage in different genomic regions of mollusks and their relationship with selective pressure has not been systematically investigated. In this study, the patterns of rare codon usage are characterized at whole genome level, and their relationship with selective pressures is investigated in Crassostrea gigas . The rare codons are enriched at the start regions of genes with high and medium expression levels, and their proportion is higher than those in the genes with low expression level. The genes with longer coding sequences and more exon numbers have lower fraction of rare codons at start regions. Rare codons have lower level of nucleotide diversity and higher frequency of rare mutations at start regions. This work is the first comprehensive investigation of the relationships between rare codon usage and some intrinsic genetic factors in mollusca species. The results suggest that the selective pressures play an important role in shaping the rare codon usage in the C. gigas genome.