Background Interleukin-23 inhibitors are novel treatment options for psoriasis, and their efficacy and safety have been widely demonstrated in phase 3 clinical trials. Nonetheless, their real-world data remain limited, especially in Asia. Objective To evaluate the real-world effectiveness of interleukin-23 inhibitor guselkumab in Chinese patients with psoriasis. Methods In this retrospective single-center study, Chinese patients with psoriasis receiving a standard dose of guselkumab from November 2018 to May 2020 were included in the study cohort. Disease assessment was performed at baseline (Week 0), and at Week 4, 12, and 20 thereafter, using Psoriasis Area and Severity Index (PASI) score. Results Data of 68 adult patients with psoriasis were retrieved for analysis. At Week 20, 72.1%/47.1% of the patients achieved PASI 90/100 response respectively, and 76.5% achieved a PASI score <3. Baseline mean PASI score was 17.5, which significantly reduced to 2.0 at Week 20 (P=0.000). No previous use of biologics was a single significant factor associated with achieving PASI 90/100 and PASI score <3 responses at Week 20 (all Ps<0.05), while there were no statistically significant differences between males and females and body weight >75 and ≤75 kg in achieving these responses (all Ps>0.05). Adverse events were experienced by five patients (7.4%), and all were mild in severity. Conclusion In this first real-world study on guselkumab among Chinese patients with psoriasis, this biologics was shown to be safe and effective in reaching an optimal clinical response up to 20 weeks.