Using microalgae to remove pharmaceuticals and personal care products (PPCPs) micropollutants (MPs) have attracted considerable interest. However, high concentrations of persistent PPCPs can reduce the performance of microalgae in remediating PPCPs. Three persistent PPCPs, namely, carbamazepine (CBZ), sulfamethazine (SMT) and tramadol (TRA), were treated with a combination of Chaetoceros muelleri and biochar in a photobioreactor during this study. Two reactors were run. The first reactor comprised Chaetoceros muelleri, as the control, and the second reactor comprised Chaetoceros muelleri and biochar. The second reactor showed a better performance in removing PPCPs. Through the response surface methodology, 68.9% (0.330 mg L−1) of CBZ, 64.8% (0.311 mg L−1) of SMT and 69.3% (0.332 mg L−1) of TRA were removed at the initial concentrations of MPs (0.48 mg L−1) and contact time of 8.1 days. An artificial neural network was used in optimising elimination efficiency for each MP. The rational mean squared errors and high R2 values showed that the removal of PPCPs was optimised. Moreover, the effects of PPCPs concentration (0–100 mg L−1) on Chaetoceros muelleri were studied. Low PPCP concentrations (<40 mg L−1) increased the amounts of chlorophyll and proteins in the microalgae. However, cell viability, chlorophyll and protein contents dramatically decreased with increasing PPCPs concentrations (>40 mg L−1).