To explore the clinical effect of modified Qinghao Qingre Ziyin decoction in the treatment of rosacea based on nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) signaling pathways. Methods A total of 70 patients with rosacea admitted to our hospital from September 2021 to March 2023 were selected as the research objects. According to the random number table method, they were divided into control group (n =35) and observation group (n =35). The control group was treated with conventional western medicine, and the observation group was treated with Qinghao Qingre Ziyin decoction on the basis of the control group. The clinical efficacy, symptom improvement, NF-κB and TNF-α signaling pathway expression levels, skin barrier function, quality of life and adverse reactions were compared between the two groups. Results The total effective rate of treatment in the observation group was 91.43%, which was higher than 71.43% in the control group (P <0.05). After treatment, the scores of dryness, itching, burning, telangiectasia and erythema in the observation group were lower than those in the control group (P <0.05). After treatment, the expression levels of NF-κB p50 and p65 mRNA and serum TNF-α levels in the observation group were lower than those in the control group (P <0.05). After treatment, the contents of epidermal sebum and stratum corneum water in the observation group were higher than those in the control group (P <0.05). After treatment, the percutaneous water loss, pH value and EI in the observation group were lower than those in the control group ,and the scores of acne symptoms, self-perception, social function and emotional function in the observation group were higher than those in the control group (P <0.05). The incidence of adverse reactions in the observation group was 11.43%, which was slightly higher than 8.57% in the control group, but the difference was not statistically significant (P >0.05). Conclusion Modified Qinghao Qingre Ziyin decoction is effective in the treatment of rosacea, which can effectively improve the symptoms of patients, promote the recovery of skin barrier function and improve the quality of life. The mechanism may be related to the regulation of NF-κB and TNF-α signaling pathways and the inhibition of inflammatory response.