两者都可指物，常可互换。其区别主要在于：(1) 引导非限制性定语从句时，通常只用which： He changed his mind, which made me very angry. 他改变了主意，这使我很生气。(2) 直接放在介词后作宾语时，通常只用which：The tool with which he is working is called a hammer. 他干活用的那个工具叫做锤子。(3) 当先行词是much, little, none, all, few, every(thing), any(thing), no(thing) 等不定代词或受其修饰时，通常用that：There was little that the enemy could do but surrender. 敌人无法，只好投降。All [Everything] that can be done must be done. 凡能做的事都必须做。(4) 当先行词受the very, the only, the same 等修饰时，通常用that：This is the only example that I know. 我知道的例子只有这一个。Those are the very words that he used. 那是他的原话。(5) 当先行词有形容词最高级或序数词 (包括last, next等)等修饰时，通常用that：This is the best dictionary that I’ve ever used. 这是我用过的最好的词典。The first thing that you should do is to work out a plan. 你应该做的第一件事是订个计划。(6) 当关系代词在定语从句中用作表语时，通常用that：China is not the country (that) it was.中国已不是过去的样子了。(7) 当先行词是一个既指人又指物的并列词组时，通常用that：They talked about the persons and things that most impressed them. 他们谈论了使他们印象最深的人和事。
(8) 当要避免重复时：Which is the course that we are to take? 我们选哪门课程？