Adamantane- and oseltamivir-resistance among influenza viruses is a major concern to public health officials. To determine the prevalence of antiviral resistant influenza viruses in Guangdong, China, 244 seasonal A(H1N1) and 222 pandemic A(H1N1) 2009 viruses were screened for oseltamivir resistance by a fluorescence-based neuraminidase (NA) inhibition assay along with NA gene sequencing. Also, 147 seasonal A(H1N1) viruses were sequenced to detect adamantane-resistance markers in M2. Adamantane-resistant seasonal A(H1N1) viruses clustering to clade 2C were dominant in 2008, followed by oseltamivir-resistant seasonal A(H1N1) viruses clustering to clade 2B during January and May 2009. In June 2009, a lineage of double-resistant seasonal A(H1N1) viruses emerged, until it was replaced by the pandemic A(H1N1) 2009 viruses. The lineage most likely resulted from reassortment under the pressure of the over use of adamantanes. As all viruses were resistant to at least one of the two types of antiviral agents, the need for close monitoring prevalence of antiviral resistance is stressed.