Objective To investigate the serum levels of Ω-3 fatty acid and hs-CRP and their clinical significance in heart failure patients with coronary heart disease (CHD). Methods Forty-three heart failure patients with CHD who were hospitalized at First Affiliated Hospital of Henan University of Science and Technology were assigned to group A, while 55 with diagnosed CHD who were concurrently hospitalized and underwent coronary angiography were assigned to group B, and 40 concurrent healthy subjects were assigned to group C. Serum levels of Ω-3 fatty acid and hs-CRP were detected in the three groups, and the correlation between serum levels of Ω-3 fatty acid and hs-CRP was analyzed. Results Serum level of Ω-3 fatty acid in group A was lower than that in groups B and C, while group B was lower than group C, and differences were statistically significant (P < 0.05). Levels of hs-CRP in group A were higher than groups B and C, while group B was higher than group C, and differences were statistically significant (P < 0.05). Correlation analyses of serum levels of Ω-3 fatty acid and hs-CRP in CHD patients and heart failure patients with CHD indicated a negative correlation between hs-CRP and serum Ω-3 fatty acid level, and had a consistent trend, and statistically significant difference (r = -0.976, P < 0.05). Conclusion Serum levels of Ω-3 fatty acid and hs-CRP were correlated with the severity of CHD.