Objective　To analyze the whole genome sequence characteristics of dengue serotype 2 virus (DENV-2) strains isolated from Guangzhou in 2023, providing new foundational data to support local dengue fever prevention and control efforts. Methods　Dengue viruses were isolated from serum samples of dengue fever patients using C6/36 cells. Whole genome sequencing of dengue virus was performed using Nanopore sequencing technology (Nanopore platform). The sequencing data were assembled utilizing IPH-NANO v1.0 software, and homology analysis, phylogenetic analysis, and amino acid site variation analysis of the dengue virus genome sequence were conducted using software such as BioEdit7.0.9.0, MEGA11, and iqTree1.6.12. Results　A total of 13 DENV-2 isolates were obtained from the serum samples of dengue fever patients in Guangzhou in 2023, all of which were derived from locally infected cases. The whole genome sequences obtained by sequencing and splicing ranged from 10 429-10 439 nt in length. The nucleotide (amino acid) homology among the 13 isolates was 99.7%-99.9% (99.6%-9.9%). A genome-wide phylogenetic analysis showed that the genotypes of all 13 Guangzhou isolates were identified as the Cosmopolitan genotype and were grouped in the same evolutionary clade as isolates from Réunion (French overseas territory), Djibouti, Kenya, and other regions. Compared with the reference sequence (NC001474), a total of 26 amino acid site variations were identified in the C/prM/E protein regions of the 13 isolates, including 4 variations in the C protein region, 8 in the prM protein region, and 14 in the E protein region. Conclusion　The DENV-2 strains isolated from Guangzhou in 2023 exhibited high homology, with closely related isolates primarily originating from countries or regions such as Réunion, Djibouti, and Kenya, it highlights the need for further assessment of the risk of dengue fever importation from East Africa, South Asia, and other regions.