Aims SHR0302 is a selective Janus kinase (JAK) 1 inhibitor under clinical investigation for the treatment of rheumatoid arthritis (RA). As SHR0302 is metabolized mainly by cytochrome P450 (CYP) 3A4, clinical studies were performed to evaluate the effects of a strong CYP3A4 inducer, rifampin, and a strong CYP3A4 inhibitor, itraconazole, on the pharmacokinetics of SHR0302 in healthy subjects. Methods Two phase I, open‐label, fixed‐sequence drug interaction studies enrolled 28 subjects. In Study A, 14 subjects received 8 mg SHR0302 on Days 1 and 10, and 600 mg rifampin once daily on Days 3–11. In Study B, 14 subjects received 4 mg SHR0302 on Days 1 and 8, and 200 mg itraconazole once daily on Days 4–10. Blood samples were collected to measure SHR0302 concentrations. Pharmacokinetic parameters were calculated using non‐compartmental analysis. Treatment comparisons were made using mixed‐effect models. Results Co‐administration with rifampin decreased the exposures of SHR0302 with geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for AUC0‐inf of 0.51 (0.49, 0.54) and Cmax of 0.91 (0.84, 0.98). Co‐administration with itraconazole increased the exposures of SHR0302 with GMR (90% CIs) for AUC0‐inf of 1.48 (1.41, 1.56) and Cmax of 1.06 (0.982, 1.14). Single oral doses of SHR0302 administered with or without rifampin or itraconazole were generally safe. Conclusions Strong CYP3A4 induction and inhibition both resulted in a weak effect on the clinical exposures of SHR0302. These present studies provided valuable information that helps inform SHR0302 dosing instructions and concomitant medication precautions.