Psoriasis, an immune-mediated chronic inflammatory skin disorder, poses challenges for topical treatment due to the thickening of the stratum corneum, hindering drug penetration. Furthermore, long-term use of chemical drugs may lead to immunosuppression and abnormal hepatic or renal dysfunction. Inspired by traditional Chinese fire cupping (Ba Huo Guan), a negative-pressure microneedle syringe therapy has been proposed here for psoriasis treatment. This microneedle syringe demonstrated an enhanced transepidermal drug delivery efficiency. Additionally, the microneedles contain nanoparticles self-assembled from Chinese herbal monomers berberine (BBR) and ferulic acid (FA), which play vital roles in psoriasis treatment, including inhibiting abnormal proliferation of local microbial communities, scavenging excess reactive oxygen species, suppressing keratinocyte proliferation locally, and modulating macrophage polarization to mitigate inflammation.