did most of his questions have nothing to do with the lessons?

这句问句本身有问题。正确的问法是：
Did most of his questions have anything to do with the lessons?

我认为这句问句是从原来的陈述句硬改而造成错误的。 （ Most of his questions had nothing to do with the lessons.)

答案是 no

No.

no

这句意思,他大多数问题与课堂上教学无关吗?答案:yes

做简单回答时，不管问句是肯定的还是否定的，只要回答是肯定的就用yes，回答是否定的就用no。不过汉语翻译出来和英语不一样而已。例如
1. Do you like the film ? (你喜欢这部电影吗？)
yes, i do ; No, i don't (是的，喜欢；不， 我不喜欢)
2. Don't you like the film ?你（你不喜欢这部电影吗？）
yes,i do （不，我喜欢）
no, i don't (是的， 我不喜欢)