Psoriasis is a common chronic skin disease characterized by hyperproliferation of keratinized cells and infiltration of inflammatory cells that affects many patients worldwide. There is no cure for psoriasis, and its pathogenesis has not yet been fully elucidated. Alterations in some TRIM family proteins have been demonstrated to be involved in the exacerbation of psoriasis, however, the molecular mechanism of TRIM14 in psoriasis is unknown. Here, we show that TRIM14 is highly expressed in psoriasis patients and is closely associated with the progression of psoriasis. A possible mechanism is that TRIM14 binds to TRAF3 and mediates the autophagic degradation of TRAF3 through the selective autophagy receptor NDP52, activating the NF-kappa B pathway. In addition, cannabidiol (CBD) can effectively inhibit the proliferation of keratinocytes, possibly by inhibiting the expression of TRIM14 and attenuating the continuous activation of the NF-kappa B pathway in psoriasis. CBD-loaded hydrogel microneedle patches significantly improved the symptoms of keratoderma thickening, erythema and desquamation in psoriatic mice and reduced the levels of inflammatory factors in psoriatic skin tissue and blood, as well as the spleen index compared with Tacrolimus cream (positive control). In summary, TRIM14, which is highly expressed in psoriasis patients, may be a potential target and provide new ideas for the treatment of psoriasis. In addition, the CBD hydrogel microneedle patches developed for TRIM14 has obvious therapeutic effects and provides a new option for future drug therapy for psoriasis patients.