Objective: The aim of present study was to prepare triamcinolone acetonide (TA) loaded NLCs hydrogel for antipsoriatic activity. Methods: A Nanostructured lipid carrier (NLCs) was prepared by using solvent diffusion and high pressure homogenization methods. NLCs dispersion was characterized by particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry, and an in vitro release study. Optimized NLC incorporated into the hydrogel and characterized for rheological properties, drug content, in vitro drug release, stability study, skin irritation and antipsoriatic activity for optimized batch of hydrogel. Results: Optimized NLCs loaded with TA were exhibited spherical shape with particle size 286±0.07 nm, polydispersity index 0.317, zeta potential-21.91±0.05mV and entrapment efficiency 86.19±0.06% respectively. The drug release of optimized batch was 8.34 % and 88.84±0.08% at 1h and 8h respectively. The release kinetics of the optimized NLCs best fitted the peppas-korsmeyer model. The results of NLC hydrogel formulations were spreadability 27.4±0.06-11.76±0.07 g. cm2/sec, drug content 65.60±0.05%-74.50±0.02%, in vitro drug release 87.52±0.04%, primary irritation index was 0.0752, it indicates barely perceptible irritation. Histopathological studies showed that, in psoriasis-induced animal treated with TA loaded NLC hydrogel, marked reduction in thickness of epidermis, as compared to conventional gel formulation. It shows the increase % orthokeratosis 88.69% and % drug activity 54.23% than the marketed formulation. Conclusion: The present results demonstrated that hydrogel based NLC shows the better and effective drug delivery for the management of psoriasis.