Using Caenorhabditis elegans as an animal model, we investigated combinational effect between 2-hydroxyatrazine (HA) and polystyrene nanoparticle (PS-NP) on function and development of D-type motor neurons. Exposure to HA (10 and 100&#
x202f;&#
x3bc;g/L) alone caused decreases in body bend, head thrash, and forward turn and increase in backward turn. Exposure to 100&#
x202f;&#
x3bc;g/L HA also caused neurodegeneration of D-type motor neurons. Moreover, combinational exposure to HA (0.1 and 1&#
x202f;&#
x3bc;g/L) induced enhancement in PS-NP (10&#
x202f;&#
x3bc;g/L) toxicity in inhibiting body bend, head thrash, and forward turn, and in increasing backward turn. In addition, combinational exposure to HA (1&#
x202f;&#
x3bc;g/L) could result in neurodegeneration of D-type motor neurons in PS-NP (10&#
x202f;&#
x3bc;g/L) exposed nematodes. Combinational exposure to HA (1&#
x202f;&#
x3bc;g/L) and PS-NP (10&#
x202f;&#
x3bc;g/L) increased expressions of
crt-1,
itr-1,
mec-4,
asp-3, and
asp-4, which govern the induction of neurodegeneration. Moreover, combinational exposure to HA (0.1 and 1&#
x202f;&#
x3bc;g/L) strengthened PS-NP (10&#
x202f;&#
x3bc;g/L)-induced decreases in
glb-10,
mpk-1,
jnk-1, and
daf-7 expressions, which encode neuronal signals regulating response to PS-NP. Therefore, our results demonstrated the effect of combinational exposure to HA and nanoplastics at environmentally relevant concentrations in causing toxic effect on nervous system in organisms.