Dengue virus infection is prevalent in tropical and sub-tropical regions of the world, which is fatal if untreated symptomatically. Emergence of new genotype within serotypes led to enhanced severity. The objective of the study is to identify the molecular characteristics of the DENV circulated during 2017 outbreak in Tamil Nadu, India and, to investigate the role of inflammatory cytokines in different ‘serotypes’ and in ‘dengue severity’. A total of 135 suspected samples were tested for DENV infection using IgM, IgG and qPCR assay; where 76 samples were positive for DENV and analysed for twelve inflammatory cytokines using ELISA. Serotyping shows 14 DENV-1, 22 DENV-2, 7 DENV-3 and 33 DENV-4, where DENV-4 was predominant. Among seventy-six, forty-two isolates were successfully sequenced for C-prM region and grouped. A lineage shift was observed in DENV-4 genotype. Irrespective of serotypes, IFNγ was significantly elevated than control and in primary infection indicating its ro