Background Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) mediates the immunity and inflammatory response in multiple ways to be intimately involved in the progression of autoimmune diseases. This study intended to explore the linkage of MALT1 with inflammation, disease activity, and its change with infliximab treatment response in Crohn's disease (CD) patients. Methods MALT1 in peripheral blood mononuclear cell samples from 72 active CD patients (at baseline, 2 weeks [W2], W6, and W12 after infliximab treatment), 20 remissive CD patients (after enrollment), and 20 healthy controls (after enrollment) were detected by RT‐qPCR. Results MALT1 was highest in active CD patients, followed by remissive CD patients, and lowest in healthy controls (p < 0.001). MALT1 was positively linked with C‐reactive protein (p = 0.001), erythrocyte sedimentation rate (p = 0.014), clinical disease activity index (p = 0.003), tumor necrosis factor (TNF)‐α (p = 0.006), interleukin (IL)‐1β (p = 0.049), and IL‐17A (p = 0.004), but not other clinical characteristics (all p > 0.05) in active CD patients. After infliximab treatment, MALT1 was decreased from baseline to W12 in active CD patients (p < 0.001), especially in responders (p < 0.001), but not in nonresponders (p = 0.053). The reduction of MALT1 at W6 (p = 0.049) and W12 (p = 0.004) was associated with a good treatment response to infliximab in active CD patients. Moreover, the response rate or MALT1 at any time point was not different between active CD patients with and without TNFi history (all p > 0.05). Conclusion MALT1 reflects aggravated inflammation and disease activity. Meanwhile, the decrement of MALT1 from baseline to W12 could reflect infliximab treatment response in CD patients.