The microalgal-bacterial symbiosis (MBS) system was promising for antibiotics removal. However, in surface water, information about MBS system for nitrogen and antibiotics removal and its interaction with antibiotics is still very limited. This study constructed a new MBS system combining Chlorella pyrenoidosa with heterotrophic nitrifying and aerobic denitrification (HN-AD) bacteria and investigated its interaction with typical antibiotics in river water, tetracycline (TC) and norfloxacin (NOR). Results showed that Optimal nitrogen removal (97.8 %–100 %) and satisfied antibiotics removal (89.3 %–95.6 %) were achieved under the microalgae-bacteria (A/B) ratio of 1/1 and inoculum dosage of 5 %. The main removal pathways of TC in river water were biodegradation and photolysis, while biodegradation and bioadsorption for NOR. Compared to the sole Chlorella pyrenoidosa or HN-AD bacteria, MBS system could provide more stable antibiotics removal and had a lower risk of cell structural damage under the pressure of TC or NOR. The TC and NOR with the background concentration level in natural water could promote the biomass growth and NH4+-N removal of MBS system. MBS system could constrain overgrowth of Chlorella pyrenoidosa. Achromobacter was the most dominant bacteria in the MBS system regardless of presence of TC and NOR.