Giant clams have economic value and play an important role in coral reef ecology. However, in recent years, giant clam resources  have been declining due to overexploitation. This study investigated the population genetic structure of giant clams (Tridacnae spp.)  in South Central and Southern Vietnam’s coast. Analysis of genetic diversity and population structure of two species of giant clams (Tridacna crocea collected in Nha Trang Bay and Con Dao and T. squamosa collected in Nha Trang Bay and Phu Quoc Island)  was done based on CO1 mitochondrial DNA. The results showed that populations of T. crocea represented the average diversity with sequence differences between individuals 0-3.5%, 10 haplotypes/30 individuals (haplotype diversity= 0.846) in Nha Trang Bay and sequence differences 0-9.7%, 16 halotypes/28 individuals (haplotype diversity=0.934) in Con Dao. Populations of T. squamosa expressed the low  diversity with the genetic sequence differences  0-2.1%, 7 haplotypes/19 individuals (haplotype diversity=0.468) in Nha Trang Bay and the  genetic sequence differences 0-1.72%, 5 halotypes/18 individuals in Phu Quoc (haplotype diversity=0.314). Phylogenetic tree did not show the specific population structure of two species from South Central and Southern coast of Vietnam. Simultaneously, populations of two species of giant clams in Vietnam had close relationship with the genetics of giant clam populations collected in some areas of Southeast  Asian coast.