Upvote:1
The toughest to catch, in pāli, are the 5 uddhambhāgiya-saṃyojana of anāgāmi: rūparāga, arūparāga, māna, uddhacca, and avijjā (in English. the five "higher fetters" which are listed here).
However, by practice, general practitioners who have never enlightened before, should focus on 5 precepts and catch immoral physical actions, first. Then he should catch 5 kāmaguna-attachment (for jhāna meditation). Then he should catch diṭṭhi vicikicchā and silabataparāmāsa (for access to insight meditation).
Upvote:3
While BonnWarapol's five higher fetters would be the most difficult to eradicate for all non-arahants, for a beginner in meditation, the hardest to eradicate would be the five hindrances (pañca nīvaraṇāni):
The commentaries by Ven. Nyanaponika Thera here or by Ven. Ajahn Brahm here, would provide more information on these. This video by Ven. Yuttadhammo Bhikkhu would also be helpful.