Q.Clear is a block sequential regularized expectation maximization penalized-likelihood reconstruction algorithm for Positron Emission Tomography (PET). It has shown high potential in improving image reconstruction quality and quantification accuracy in PET/CT system. However, the evaluation of Q.Clear in PET/MR system, especially for clinical applications, is still rare. This study aimed to evaluate the impact of Q.Clear on the 18F-fluorodeoxyglucose (FDG) PET/MR system and to determine the optimal penalization factor β for clinical use.A PET National Electrical Manufacturers Association/ International Electrotechnical Commission (NEMA/IEC) phantom was scanned on GE SIGNA PET/MR, based on NEMA NU 2-2012 standard. Metrics including contrast recovery (CR), background variability (BV), signal-to-noise ratio (SNR) and spatial resolution were evaluated for phantom data. For clinical data, lesion SNR, signal to background ratio (SBR), noise level and visual scores were evaluated. PET images reconstructed from OSEM + TOF and Q.Clear were visually compared and statistically analyzed, where OSEM + TOF adopted point spread function as default procedure, and Q.Clear used different β values of 100, 200, 300, 400, 500, 800, 1100 and 1400.For phantom data, as β value increased, CR and BV of all sizes of spheres decreased in general; images reconstructed from Q.Clear reached the peak SNR with β value of 400 and generally had better resolution than those from OSEM + TOF. For clinical data, compared with OSEM + TOF, Q.Clear with β value of 400 achieved 138% increment in median SNR (from 58.8 to 166.0), 59% increment in median SBR (from 4.2 to 6.8) and 38% decrement in median noise level (from 0.14 to 0.09). Based on visual assessment from two physicians, Q.Clear with β values ranging from 200 to 400 consistently achieved higher scores than OSEM + TOF, where β value of 400 was considered optimal.The present study indicated that, on 18F-FDG PET/MR, Q.Clear reconstruction improved the image quality compared to OSEM + TOF. β value of 400 was optimal for Q.Clear reconstruction.© 2022. The Author(s).